Author and Contributing Experts to this Guide include:
La enfermedad de Huntington (EH) es un trastorno genético progresivo y poco común, en el que las células nerviosas, en ciertas partes del cerebro, se degeneran a lo largo de los años. Afecta de manera mental y física, y aunque los síntomas pueden ser tratados, esta condición no tiene cura, lo que eventualmente causa la muerte.
¿Qué es la enfermedad de Huntington?
EH es una enfermedad neurodegenerativa, lo que significa que ataca las células nerviosas. Es principalmente una condición hereditaria, pasada de generación a generación, aunque en algunos casos poco comunes, ocurre espontáneamente y sin antecedentes familiares.
La aparición adulta es la forma más común de EH. Las personas con este tipo generalmente desarrollan síntomas en sus 30 o 40 años 1. Los primeros síntomas pueden incluir pequeños movimientos involuntarios, cambios de humor, problemas cognitivos y problemas o dificultad para tomar decisiones.
Muchas personas también desarrollan movimientos involuntarios de espasmos conocidos como corea. A medida que los síntomas progresan, las personas afectadas presentan problemas para caminar, hablar, tragar, y realizar tareas simples del día al día.
Una forma menos común es la EH de inicio temprano, a veces llamada EH juvenil, que afecta a un menor número de personas y generalmente comienza en la infancia o adolescencia.
La EH progresa lentamente, lo que resulta en una expectativa de vida de 10 a 25 años a partir del diagnóstico. La forma juvenil progresa mucho más rápido, causando que los pacientes fallezcan en diez años o menos.
Si bien los médicos pueden tratar los síntomas, por el momento no hay ninguna forma de detener la progresión de la EH.
La enfermedad de Huntington afecta aproximadamente 3 a 7 personas de cada 100,000 de ascendencia europea, y es menos común en otras poblaciones, incluyendo las personas de ascendencia japonesa, china y africana. En general, alrededor de 41,000 estadounidenses tienen síntomas de HD, y otros 200,000 corren el riesgo de heredarla.
¿Qué causa la enfermedad de Huntington?
La enfermedad de Huntington es causada por una repetición expandida de los nucleótidos "CAG" en el gen de la huntingtin (HTT) en el brazo corto del cromosoma 4. El gen HTT provee instrucciones para producir una proteína llamada huntingtin.
Esta proteína es un factor fundamental en las células nerviosas del cerebro, también conocidas como neuronas.
Todos tenemos el gen HTT con una sección de repeticiones CAG. Para las personas con enfermedad de Huntington, esta repetición ocurre más veces de lo necesario para la función normal. Normalmente, esta sección de ADN se repite alrededor de 10 a 28 veces; sin embargo, en personas con EH, se repite entre 36 y 120 veces.
En última instancia, la serie de repeticiones crea una cadena de proteínas que es demasiado larga para que el cuerpo pueda manejarla. Cuando esto sucede, la proteína que es excesivamente larga se corta en fragmentos más pequeños.
Sin embargo, estos fragmentos son dañinos y terminan adhiriéndose unos a otros, y obstruyendo la neurona. Esto causa que las células mueran e induce la progresión de la EH.
Cuando una persona con la enfermedad de Huntington tiene un hijo, hay un 50% de posibilidades de que su hijo también tenga EH. A veces, cuando la repetición se transmite al niño/a, se acumulan más repeticiones.
Este fenómeno genético se llama anticipación y se ve más comúnmente cuando la copia dañina de HTT se transmite del padre. Esto es importante porque existe una correlación entre el número de repeticiones y la edad de aparición de los síntomas.
“Todas las personas tienen dos copias del gen de Huntington y cuando una de esas copias tiene mas repeticiones de lo que tiene que ser, o se expande, el gen no puede funcionar correctamente. Eso es lo que hace que los síntomas de la condición aparezcan”, explicó Fallon Brewer, asesora genética principal de la Universidad de Alabama en Birmingham.
"Todas las personas con el alelo expandido desarrollarán síntomas en algún momento, a veces no se presentan hasta los cuarenta, cincuenta o sesenta años, y tal vez incluso más tarde. Muchas veces, las personas tienen hijos mucho antes de saber que tienen esta condición. Simplemente no son sintomáticos. Aunque es algo con lo que nacieron y tuvieron toda su vida, en la mayoría de los casos se necesitan muchas décadas para que aparezcan síntomas”, agregó.
La enfermedad de Huntington se hereda en un patrón autosómico dominante. Esto significa que una persona necesita sólo una copia del gen con una expansión dañina para desarrollar EH.
De modo que si uno de los padres tiene EH, hay un 50% de posibilidades de heredar la expansión anormal del gen. Si usted obtiene el gen de sus padres, puede transmitirlo a sus hijos, y también tendrán un 50% de posibilidades de desarrollar la enfermedad.
Si no obtiene el gen de sus padres, no será transmitido a sus hijos.
Las personas con repeticiones de 27 a 35 CAG no tendrán ningún síntoma de EH pero corren el riesgo de transmitir una repetición mayor a sus hijos. Cuando una persona tiene 36-39 repeticiones CAG, entonces caen en un área gris.
Se dice que estos individuos tienen una penetrancia reducida, lo que significa que si bien llevan una copia expandida del gen HTT, es posible que no presenten ningún síntoma. Si una persona hereda 40 o más repeticiones, desarrollará EH en algún momento de su vida. Individuos con la forma juvenil de HD tienden a tener más de 60 repeticiones.
Etapas de la enfermedad de Huntington
La mayoría de los investigadores creen que la gravedad de la enfermedad y la rapidez con que progresa están relacionadas con la cantidad de repeticiones de CAG en el gen HTT.
Los pacientes con menos repeticiones de CAG demuestran síntomas cuando son mayores. También tienen una progresión más lenta y menor gravedad de los síntomas. Esto afectará la duración de cada etapa de la enfermedad en cada paciente.
La enfermedad de Huntington se divide en diferentes etapas de progresión.
Etapa 1: etapas iniciales
Durante la etapa inicial, después de que un paciente ha sido diagnosticado con la enfermedad de Huntington, generalmente puede continuar trabajando y participando en actividades normales. Se puede notar cierta torpeza, movimientos oculares anormales, cambios de actitud y manifestaciones psiquiátricas como ansiedad o depresión.
Etapa 2: Etapa intermedia
Durante las etapas intermedias, la corea, que son movimientos irregulares e involuntarios, comienza a desempeñar un papel más importante en la vida cotidiana. Este cambio en los movimientos, junto con la debilidad en el cuerpo y el aumento de la dificultad para hablar y tragar, conducen a una disminución en la capacidad de completar las tareas cotidianas.
Esto puede llevar a que los pacientes abandonen sus trabajos, pero aún pueden continuar completando actividades de cuidado personal. Además de los cambios físicos, puede haber un aumento en los comportamientos agresivos y cambios generales en el funcionamiento social.
Etapa 3: Etapas tardías
Durante las últimas etapas de la EH, el paciente depende de las personas que lo cuidan. Comúnmente la persona experimentará una gran pérdida de peso y no podrá caminar ni hablar. En esta etapa, la deglución puede ser muy difícil y existe un grave riesgo de asfixia.
Esta etapa también se caracteriza por períodos de confusión y gritos. Los síntomas psiquiátricos pueden ocurrir, pero son más difíciles de reconocer y tratar en esta etapa de la enfermedad, debido a las dificultades de comunicación.
Las personas con la enfermedad de Huntington generalmente mueren entre 15 y 20 años después del primer inicio de los síntomas. La causa real de muerte suele ser debido a una complicación de la enfermedad y puede incluir neumonía, insuficiencia cardíaca o infecciones.
Señales y síntomas de la enfermedad de Huntington
En cada etapa de la enfermedad de Huntington aparecen diferentes síntomas. Estos se pueden subdividir aún más en trastornos del movimiento, cognitivos y psiquiátricos. En aproximadamente ⅔ de pacientes, los primeros síntomas son cognitivos 2.
Los síntomas que aparecen primero pueden variar ampliamente de un paciente a otro y la gravedad de cada síntoma también. Esto significa que las habilidades funcionales de cada persona serán diferentes.
Trastornos de movimiento
Los trastornos del movimiento pueden incluir problemas de movimientos involuntarios y deficiencias en los movimientos voluntarios, como:
- Sacudidas bruscas o retorcimientos, y movimientos rápidos y repentinos de los brazos, piernas, cara y otras partes del cuerpo (corea de Huntington). La corea está presente en más del 90% de los pacientes. Se vuelve más grave durante los primeros 10 años. Los movimientos siempre están presentes durante las horas de vigilia y empeoran con el estrés.
- Problemas musculares, como rigidez o contractura muscular (distonía)
- Movimientos oculares lentos o anormales, que incluyen girar la cabeza para cambiar la posición del ojo
- Marcha, postura y equilibrio deteriorados o inestables, incluyendo "saltos" al caminar.
- Dificultad para hablar o tragar.
- Deficiencia de los movimientos voluntarios, causando un gran impacto en la capacidad para trabajar, realizar actividades diarias, comunicarse y permanecer independiente.
- Disfunción olfatoria
- Movimientos faciales, incluyendo muecas
- Movimientos lentos e incontrolados
- Caídas provocadas por los movimientos anormales
"A veces se refiere a la enfermedad de Huntington como ‘corea de Huntington’, lo cual es en realidad uno de los síntomas claves para diagnosticar clínicamente a alguien con esta condición", dijo Brewer.
"Especialmente en las primeras etapas, en nuestros pacientes, no vemos demasiados cambios en los primeros años. En general el movimiento comenzará a empeorar y se volverá más pronunciado con el paso del tiempo. Comenzarán a tener más problemas de equilibrio y a caerse más. Los síntomas de estado de ánimo pueden volverse más frecuentes. Pueden volverse menos manejables”, agregó Hope Heller, una trabajadora social clínica con licencia en el área metropolitana de DC, que ha trabajando con la comunidad de la enfermedad de Huntington durante los últimos 10 años.
Todos los pacientes con EH experimentan cambios cognitivos que empeoran progresivamente con el tiempo.
Esos impedimentos cognitivos pueden incluir:
Demencia que empeora lentamente, que incluye:
* Desorientación o confusión. * Pérdida de juicio * Pérdida de memoria * Cambios de personalidad * Cambios en el habla, incluyendo pausas al hablar
Degeneración de neuronas en el caudado y el putamen, así como en la corteza cerebral
Dificultad para organizar, priorizar o concentrarse en tareas
Falta de flexibilidad o tendencia a atascarse en un pensamiento, comportamiento o acción (perseverancia)
Cambios regionales y de todo el cerebro en la materia gris y blanca, con atrofia progresiva de la materia gris y blanca muchos años antes de la aparición prevista
Las funciones del lenguaje están en un nivel disminuido de complejidad sintáctica, y hay anormalidades del habla cortical. En las últimas etapas, es común tener dificultades para identificar o encontrar palabras.
Falta de control de los impulsos que puede provocar arrebatos, actuar sin pensar y promiscuidad sexual.
El sueño y los ritmos circadianos se alteran, posiblemente como resultado de la disfunción hipotalámica y / o alteraciones en la secreción de melatonina
Pérdida de neuronas en el globus pallidus, núcleo subtalámico, tálamo, hipotálamo, sustancia negra e hipocampo.
Falta de conciencia de los comportamientos propios y habilidades.
Habilidades visuoespaciales deterioradas
Deterioro de la capacidad para manipular los conocimientos adquiridos.
Lentitud en el procesamiento de pensamientos o "encontrar" palabras
Pérdida de peso
Alteración del metabolismo del colesterol.
Dificultad para aprender nueva información.
“Algunas de las primeras señales o síntomas pueden incluir cosas como depresión e irritabilidad, falta de coordinación o problemas para aprender nueva información o tomar decisiones. Pero es importante saber que estos síntomas iniciales que no son muy específicos y también se pueden observar en personas que no tienen la enfermedad de Huntington", dijo Brewer.
El trastorno psiquiátrico más común asociado con la enfermedad de Huntington es la depresión. A veces este es un tema difícil de separar.
Es probable que las personas que enfrentan este diagnóstico experimenten ansiedad y depresión. Sin embargo, la depresión y la ansiedad asociadas con la EH parecen estar directamente relacionadas con los cambios en el funcionamiento del cerebro. Algunos signos de depresión relacionada con la EH incluyen:
- Sentimientos de irritabilidad, tristeza o apatía.
- Retiro social
- Fatiga y pérdida de energía.
- Pensamientos frecuentes de muerte o suicidio.
Otros trastornos psiquiátricos comunes incluyen:
- Trastorno obsesivo compulsivo, una condición marcada por pensamientos recurrentes, intrusivos y comportamientos repetitivos.
- Manía, que puede causar un estado de ánimo elevado, hiperactividad, comportamiento impulsivo y autoestima elevada.
- Ansiedad, estrés y tensión.
- Trastorno bipolar, una afección con episodios alternos de depresión y manía.
- Alteraciones del comportamiento
- Mal humor
- Psicosis, incluyendo psicosis afectiva o psicosis esquizofrénica.
- Explosividad intermitente y agresión.
- Abuso de alcohol
- Disfunción sexual y desviaciones
- Delirios, a menudo paranoicos
“Los síntomas iniciales tienden a ser en gran medida cognitivos o psiquiátricos y relacionados con el estado de ánimo. La depresión y la ansiedad pueden ser signos tempranos de Huntington. Pero no quiero que las personas que están en riesgo piensen que solo porque tienen depresión y ansiedad, significa que están en las primeras etapas", dijo Heller
“Realmente buscamos resolver los cambios de personalidad y los cambios de humor más grandes. Si alguien de repente está más irritable de lo que solía ser, tiene peor temperamento o de repente se vuelve más empático, la depresión y la ansiedad pueden comenzar a realmente salirse de control", agregó.
No hay mucha diferencia en el tratamiento de los primeros síntomas psiquiátricos de EH con el de las personas que tienen síntomas similares sin tener EH. Sin embargo, la intervención temprana es clave porque el tratamiento y el manejo temprano de los síntomas conduce a una mejor calidad de vida en general, especialmente para alguien en las primeras etapas de la EH.
“Muchas veces recibo llamadas de madres jóvenes que están en riesgo, o que son genéticamente positivas y se sienten más olvidadizas o tienen más dificultades para manejar las cosas. Pero con todo lo que sucede a diario y como madre de niños pequeños, yo siempre las tranquilizo, porque no quiero que alguien que esté en riesgo o sepa que tenga un gen positivo piense repentinamente, oh Dios mío, ya estoy mostrando signos.
“Aunque hay signos tempranos, generalmente se buscan problemas de equilibrio, como si la persona comienza a caerse o si de repente andar en bicicleta se vuelve más difícil. Es una enfermedad de progresión relativamente lenta, dependiendo de la edad general de inicio.
No se van a ver cambios durante semanas o meses, frecuentemente se verán los cambios de meses a años”, agregó Heller.
Los problemas psiquiátricos son una preocupación constante y preocupante para los proveedores de atención médica.
“Verás un cambio en los síntomas psiquiátricos con el tiempo. A veces, a medida que la condición progresa, los síntomas pueden mejorar un poco. A veces pueden empeorar. Y siempre existe la preocupación con el control de los impulsos y la depresión, sobre el alto riesgo de suicidio”, señaló Heller.
Hay ciertos hitos claves en los que los proveedores médicos son más cautelosos.
“En mi experiencia, la primera conversación más difícil que tenemos con un paciente es el diagnóstico. Y a veces la conversación aún más difícil es cuando les decimos "ya no deberías conducir más", dijo Heller.
A medida que la EH avanza, los pacientes reaccionan con más lentitud y su juicio puede verse afectado debido a los movimientos.
“Puede que estés conduciendo de forma más brusca. Hay muchos factores que pueden afectar y muchas veces la persona dirá: ‘Bueno, tengo mi radio apagado. Estoy muy concentrado".
“Honestamente, no se trata de lo que estás haciendo mientras conduces. Se trata de si un niño patea la pelota en la calle, ¿es su tiempo de reacción lo suficientemente rápido como para frenar? O si otro auto te detiene, ¿es tu tiempo de reacción lo suficientemente rápido? dijo Heller.
Síntomas de la enfermedad de Huntington juvenil
El inicio y la progresión de la EH en personas más jóvenes puede ser ligeramente diferente a la de los adultos.
La EH juvenil se define como la aparición de síntomas antes de los 20 años. Representa hasta el 10% de las personas con EH. Deterioro mental severo, síntomas motores y cerebelosos prominentes, retraso en el habla y el lenguaje, y un detrimento rápido es común en pacientes con EH juvenil.
Los síntomas de inicio temprano pueden incluir:
- Cambios de comportamiento
- Dificultad para prestar atención
- Una disminución rápida y significativa en el rendimiento escolar
- Problemas de comportamiento
- Cambios físicos
- Músculos contraídos y rígidos que afectan la marcha (especialmente en niños pequeños)
- Temblores o movimientos involuntarios leves.
- Caídas frecuentes o torpeza.
Prevalencia y factores de riesgo para la enfermedad de Huntington
Huntington no es una enfermedad discriminatoria, lo que significa que no sucede en un género o un grupo de edad específico, aunque la mayoría de los pacientes tienen entre 30 y 50 años durante el inicio de los síntomas. Todo se reduce a si alguien lleva o no una copia expandida del gen HTT.
“La enfermedad de Huntington afecta a entre tres y siete por cada 100,000 personas de ascendencia europea. Sin embargo, hay algunos lugares en América del Sur, como Venezuela, por ejemplo, donde la prevalencia general de EH es de aproximadamente uno en 20,000, por lo que es un poco más común. Un área particular en Maracaibo, que se encuentra en Venezuela, tiene una prevalencia mucho mayor de aproximadamente siete casos por cada 100 personas”, dijo Fallon.
Por el contrario, hay poblaciones en las que es menos común, como las personas de ascendencia japonesa, china o africana.
Huntington no es algo que normalmente sucede en niños pequeños. Si ocurre en niños, generalmente comienza a fines de la adolescencia y a principios de los 20 años y progresa mucho más rápido que cuando se presenta en adultos.
Diagnóstico de la enfermedad de Huntington
Inicialmente, si se sospecha la enfermedad de Huntington debido a antecedentes familiares, un médico comenzará con un cuestionario simple y un examen físico para enfocarse en sus síntomas. La historia familiar es importante, pero un análisis adicional es esencial.
Los médicos buscarán síntomas físicos como cambios en sus habilidades motoras, equilibrio y reflejos que involucren su coordinación. También lo examinarán para detectar cualquier cambio sensorial en su salud mental o psiquiátrica.
Los movimientos y comportamientos anormales son uno de los signos reveladores de Huntington, así que sea completamente sincero y honesto con su médico sobre cualquier cambio notable.
“Hay dos piezas diferentes para un diagnóstico. Es en gran parte un diagnóstico clínico y eso es diferente de las pruebas genéticas.
“Se puede pasar por el proceso de pruebas genéticas y descubrir que se tiene la mutación genética, pero eso no es un diagnóstico. Solo porque le hayan dicho que tiene el gen, no le han diagnosticado. El diagnóstico es clínico. Se basa en componentes psiquiátricos y síntomas motores", dijo Heller.
La comunidad médica no está de acuerdo a veces sobre cómo diagnosticar oficialmente la EH. Y la manera en la que se diagnostica ha cambiado con los años.
"Se vería a un especialista en EH o un neurólogo o un neuropsiquiatra y ellos examinarían sus síntomas y los antecedentes familiares. Y si tiene antecedentes familiares conocidos, técnicamente podría recibir un diagnóstico clínico sin pruebas.
“Antes de 1993, no había una prueba genética fácilmente accesible. Por lo tanto, las personas fueron diagnosticadas en gran medida solo con antecedentes familiares y síntomas", agregó Heller.
La combinación de pruebas clínicas y genéticas es ahora el mejor curso de acción para el diagnóstico.
“Siempre es bueno confirmar un diagnóstico con pruebas genéticas. Y se realiza un diagnóstico genético enviando una muestra de sangre del paciente a un laboratorio que ofrece pruebas de EH. Ese laboratorio de pruebas realizará un análisis para determinar el número de repeticiones CAG para cada uno de los alelos de Huntington del individuo. Entonces, si uno de esos números repetidos es de 40 o más, eso confirmaría un diagnóstico de HD", dijo Brewer.
La Sociedad de Enfermedades de Huntington de América (HDSA) ofrece un proceso de prueba recomendado dirigido a alguien que está en riesgo según los antecedentes familiares, pero ellos mismos no muestran ningún signo o síntoma.
Puede hacerse una prueba genética si tiene antecedentes familiares de la enfermedad pero no tiene síntomas. Esto se llama prueba predictiva.
La prueba no puede decirle cuándo comenzará la enfermedad o qué síntomas aparecerán primero.
“Pasan por un protocolo de prueba predictivo, que generalmente implica una consulta de asesoramiento genético, una evaluación psicológica, un examen neurológico y luego una extracción de sangre. Si bien los pasos pueden variar de un centro a otro o de un lugar a otro, ese es el tipo de modelo presentado por HDSA y recomendado para seguir”, agregó Brewer.
Un médico puede ordenar pruebas de imágenes cerebrales, como una resonancia magnética o tomografías computarizadas que muestran imágenes detalladas del cerebro.
Estas imágenes pueden revelar cambios en el cerebro en áreas afectadas por la enfermedad de Huntington, pero que no aparezcan en las faces iniciales de la enfermedad. Estas pruebas también se pueden usar para descartar otras condiciones que pueden estar causando los síntomas.
Algunas personas con antecedentes familiares de EH prefieren conocer su riesgo antes de comenzar a planificar una familia. Las pruebas de ADN para detectar el gen anormal en el cromosoma 4 pueden ayudarlo a prepararse para el futuro.
Una parte fundamental de esto es reunirse con un asesor genético para que pueda discutir y comprender completamente los pros y los contras de las pruebas.
Para las personas con la repetición HTT expandida, hay varias opciones disponibles para la planificación familiar:
- Tener hijos de la manera "tradicional". Hay un 50% de posibilidades de que el niño herede la repetición y también desarrolle EH en su futuro.
- Para las familias que desean asegurarse de que su hijo no se vea afectado, podrían someterse a una fertilización in vitro seguida de un diagnóstico genético previo a la implantación. Los embriones se examinarían para la repetición y solo los embriones sin la repetición se colocarían en el útero de la madre.
- Durante el embarazo, una amniocentesis o una prueba de CVS pueden revelar si el feto tiene la repetición de CAG o no. Si el niño lleva la repetición, se considerarán opciones adicionales como la terminación del embarazo.
- Donación de óvulos o donación de esperma
Al igual que con todos los tipos de pruebas de ADN, hay ciertas ventajas y limitaciones que acompañan los resultados. Por ejemplo, saber si es portador hace que sea más fácil prepararse para el futuro y educarse sobre la enfermedad y sus síntomas.
Sin embargo, para algunas personas, tener esta información puede generar ansiedad. Saber que más adelante en la vida desarrollarán EH, una condición para la que actualmente no hay cura, puede ser frustrante y aterrador.
Para las mujeres que ya están embarazadas, se puede evaluar al niño a través de una amniocentesis. Después de que nazca el niño, no se recomienda someterlo a pruebas hasta que tenga 18 años.
Normalmente, la EH es una condición de inicio en adultos, y no se recomienda someterse a pruebas hasta que se pueda obtener el consentimiento informado de la persona.
Opciones de tratamiento y atención para pacientes con la enfermedad de Huntington
Actualmente no existe cura para la enfermedad de Huntington, pero hay opciones de tratamiento que ayudan a disminuir los síntomas.
Sin embargo, los investigadores se mantienen optimistas respecto esto.
“Si bien aún no tenemos una cura para la enfermedad de Huntington, nos estamos acercando cada vez más. Hoy tenemos tratamientos sintomáticos que pueden ayudar, y también estamos construyendo desde un punto de vista científico, cosas para crear una cura que nos da mucha esperanza para el futuro", dijo el Dr. Victor Sung, neurólogo de la Universidad de Alabama en Birmingham. Sung es el director de la clínica de enfermedades de Huntington, que ha sido designada como uno de los Centros de Excelencia de la nación por HDSA.
El Dr. Sung agregó: “Debido a los aspectos genéticos de la enfermedad, tengo pacientes con otras enfermedades como el Alzheimer o la enfermedad de Parkinson que tienen mucha más notoriedad pública, y ciertamente mucha más gente las padece.
"Pero no tenemos una buena idea de cuál es la causa exacta de la enfermedad de Parkinson o cuál es la causa exacta de la enfermedad de Alzheimer". Y cuando no tienes eso, es difícil atacar una enfermedad y curarla.
“Sin embargo, para la enfermedad de Huntington, sabemos cuál es la causa. La causa es ese gen mutado y todas las cosas que salen de él. Entonces, es tan simple y tan complejo como evitar que ese gen mutado haga lo que quiere hacer.
Y es curioso, a principios de los 1990, cuando el gen finalmente fue secuenciado, mucha gente sintió que en 5 o 10 años tendríamos una cura para la enfermedad de Huntington. Pero ha resultado mucho más difícil que eso".
Sin embargo, la ciencia y la búsqueda de una cura para la enfermedad de Huntington se han acelerado. Sung sigue siendo realista sobre lo que se aproxima.
"Hay múltiples estrategias de tipo curativo o modificadoras que actualmente se están investigando en humanos. Estamos más cerca que nunca. Y creo que sí, hay cosas emocionantes de las que todos quieren hablar, como CRISPR y cosas así. Estos aún están siendo investigados en modelos animales.
“Me encantaría que CRISPR se vuelva una realidad, pero la verdad es que todavía está lejos para los humanos con la enfermedad de Huntington.
“Pero en este momento tenemos otras tecnologías que se están investigando en seres humanos con la enfermedad de Huntington. Uno de ellos está en la tercera fase de prueba, que es el último paso necesario antes de conseguir la aprobación de la FDA. Así que eso es lo más cerca que se puede estar", dice el Dr. Sung.
Hasta que esto suceda, el mejor curso de acción es tratar varios síntomas de la EH para que los pacientes puedan vivir lo más cómodos posible después del diagnóstico.
Debido a que la EH afecta diferentes aspectos del cuerpo de una persona, existen numerosos tratamientos que los médicos pueden probar, incluyendo:
La corea de Huntington, que son los movimientos corporales incontrolables, a menudo se trata con fisioterapia, amantadina y tetrabenazina, aunque los fármacos antipsicóticos son una opción si la tetrabenazina no funciona. Los posibles efectos secundarios incluyen somnolencia, inquietud y el riesgo de empeorar o desencadenar depresión u otras afecciones psiquiátricas. Otros medicamentos que pueden ayudar a suprimir la corea incluyen levetiracetam y clonazepam, pero los efectos secundarios pueden limitar su uso.
Los antidepresivos, los estabilizadores de estado de ánimo y los medicamentos antipsicóticos se administran comúnmente para ayudar con los trastornos psiquiátricos causados por Huntington en los que los pacientes no pueden controlar los cambios emocionales y cognitivos. Los medicamentos antipsicóticos como la quetiapina, la risperidona y la olanzapina pueden suprimir los arrebatos violentos, la agitación y otros síntomas de trastornos del estado de ánimo o psicosis. Pero estas drogas también pueden causar diferentes trastornos del movimiento. Los medicamentos estabilizadores del estado de ánimo pueden ayudar a prevenir los altibajos asociados con el trastorno bipolar e incluyen anticonvulsivos como Divalproex y carbamazepina.
La psicoterapia, la terapia del habla y la terapia ocupacional pueden ayudar a mejorar la calidad de vida y limitar la cantidad de ayuda externa que necesita una persona con la enfermedad.
La terapia del habla puede ayudar a mejorar la comunicación afectada por los músculos de la garganta y la boca que son esenciales para el habla, la deglución y la alimentación.
La fisioterapia puede ayudar a mantener la movilidad por el mayor tiempo posible al enseñarle ejercicios que mejoran la fuerza, flexibilidad, equilibrio y coordinación.
La terapia ocupacional puede ayudar al paciente con la enfermedad de Huntington, a los miembros de la familia y a los cuidadores a utilizar dispositivos de asistencia, como pasamanos o dispositivos para bañarse, vestirse, comer y beber.
Debido a que los pacientes con EH tienen dificultades para mantener un peso saludable, la terapia nutricional también es un curso de tratamiento recetado por los médicos. El esfuerzo físico o problemas metabólicos del paciente pueden causar necesidades calóricas más altas, y como resultado se pueden requerir más comidas al día o el uso de suplementos dietéticos.
El tratamiento también puede implicar la participación de entidades de apoyo, incluyendo organizaciones sin fines de lucro como el Huntington's Disease Society of America, o agencias de servicios sociales o de salud locales y estatales que pueden brindar atención diurna a personas con la enfermedad, programas de asistencia alimentaria o un descanso para las personas que cuidan del paciente.
“Hay dos medicamentos aprobados por la FDA en los Estados Unidos que tratan los síntomas motores de la corea de esta enfermedad, y son tratamientos muy efectivos. Además de eso, también hay otros medicamentos que se usan fuera de etiqueta para tratar los síntomas motores”, comentó el Dr. Sung.
No todos los tratamientos funcionan para todos los pacientes. Los médicos recetarán tratamientos específicos según lo consideren adecuado a medida que los síntomas progresen. Además, los medicamentos irán evolucionando con el tiempo y, en algunos casos, aquellos medicamentos que tratan ciertos síntomas pueden terminar provocando efectos secundarios que empeoran otros síntomas.
"Hay cambios estructurales y químicos en el cerebro causados por la enfermedad de Huntington, y en algunos aspectos, esos síntomas de comportamiento se pueden tratar, incluso más eficazmente, en la enfermedad de Huntington de lo que se tratan en una persona que solo tiene depresión".
“Si podemos mejorar los síntomas de comportamiento, irritabilidad, impulsividad, ira o agresión, depresión, ansiedad, o cualquiera de los síntomas que está causando un gran problema, eso también puede tener un impacto muy positivo en el paciente y la familia”, agregó el Dr. Sung.
Durante las etapas tempranas e intermedias de la enfermedad, cuando los síntomas aún son impactantes pero no abrumadores, los tratamientos médicos como medicamentos y terapias pueden ayudar a los pacientes a mantener su independencia.
La depresión y el suicidio son comunes entre las personas con EH. Por eso es importante que los cuidadores controlen los síntomas y busquen ayuda médica para la persona inmediatamente, cuando sea necesario.
Una vez que la enfermedad llega a la etapa tardía, es probable que los pacientes necesiten atención continua en el hogar o en un centro calificado.
Prevención de la enfermedad de Huntington
No hay una forma real de prevenir la enfermedad de Huntington después de que una persona haya nacido. Se puede nacer con el gen HTT expandido o no.
La única forma de prevenir la enfermedad es a través de estrategias de pruebas genéticas y opciones de planificación familiar. Si usted es un padre afectado, un asesor genético puede analizar los riesgos potenciales asociados con EH y otras alternativas.
Las parejas deben decidir si quieren tiener hijos o no, o si deben considerar métodos como la fertilización in vitro con óvulos o esperma de donantes, u otras opciones similares.
Pronóstico de la enfermedad de Huntington
La enfermedad de Huntington siempre es mortal, y tiene una expectativa de vida promedio de 15 a 20 años después de el diagnóstico inicial. La enfermedad de Huntington juvenil generalmente produce la muerte dentro de los 10 años posteriores al inicio de los síntomas.
Hacer frente a un diagnóstico y tratamiento es fundamental para mejorar la calidad de vida de la persona para el futuro.
Las causas comunes de muerte por EH incluyen:
- Neumonía u otras infecciones
- Lesiones relacionadas con caídas.
- Complicaciones relacionadas con la incapacidad para tragar
El número de repeticiones de CAG puede determinar la gravedad de los síntomas. Las personas con pocas repeticiones pueden tener movimientos anormales leves más adelante en la vida y una progresión lenta de la enfermedad.
Los pacientes con una cantidad más alta de repeticiones pueden verse gravemente afectados a una edad más temprana.
“La comunidad de la enfermedad de Huntington, desde un punto de vista de apoyo, tiene una presencia en línea muy fuerte, desde los grupos de apoyo en línea hasta los grupos de Facebook y ese tipo de cosas. Por lo tanto, comuníquese con la comunidad y realmente será aceptado. Ellos lo ayudarán a conectarse y a acceder a los recursos que hay disponibles localmente.
“Entre todas las organizaciones clínicas y de investigación para la enfermedad de Huntington, existe un alcance que cubre realmente la mayor parte de los Estados Unidos y la mayor parte del mundo. Así que simplemente busque y conéctese con un centro, ya sea un centro de investigación o un centro clínico, hay personas allí que pueden ayudarlo”, dijo el Dr. Sung.
“Si quieres ser parte de la investigación hacia una cura, hay oportunidades para participar. Hay varios ensayos de fase dos en curso que, con suerte, si tienen éxito, también pasarán a la fase tres en los próximos años. Entonces, hay cosas muy pronto.
“Hay muchas oportunidades para involucrarse y muchas oportunidades para obtener ayuda para lidiar con todo lo que está pasando ahora y en el futuro también. El mensaje es que no está solo y hay toneladas de sitios web donde las personas pueden encontrar recursos donde pueden obtener ayuda y obtener respuestas a sus preguntas”, agregó el Dr. Sung.
Puede obtener más información sobre los ensayos de investigación actuales visitando clinicaltrials.gov.
Qué hacer a continuación: viviendo con la enfermedad de Huntington
La enfermedad de Huntington progresa durante varios años y afecta a cada persona de manera diferente. Por lo tanto, vivir con la condición variará según los síntomas y el grado de progresión.
Sin embargo, debido a que no hay cura y la condición es fatal, es esencial anticipar qué se necesitará atención en las etapas avanzadas de la enfermedad. Cuanto antes se lleven a cabo estas discusiones, mayor será la participación del paciente en ayudar a tomar estas decisiones.
Debe incluir asesoramiento genético y su médico en estas discusiones para que sepa exactamente qué esperar.
Crear directivas sobre el final de vida y documentos de sucesión puede ayudar a facilitar la transición para los miembros de la familia. Evitan conflictos en una fecha posterior.
Específicamente, se deberán atender temas como los centros de atención, el cuidado de hospicio y el contenido del testamento en vida. También se deberán dar instrucciones por adelantado, para que el paciente pueda capacitar a las personas adecuadas para tomar decisiones cuando el/ella ya no pueda hacerlo.
Además, considere participar en varios grupos de apoyo que le pueden ayudar a guiar sus elecciones y proporcionar recursos a lo largo del tiempo. Actualmente hay 50 centros de excelencia en los Estados Unidos para la enfermedad de Huntington.
Puede ir a Huntington's Disease Society of America para encontrar un centro cerca de usted.
Huntington's Disease Society of America (HDSA) 505 Eighth Avenue Suite 902 New York NY 10018 Phone: 800-345-4372 (toll-free); 212-242-1968 Fax: 212-239-3430 Email: firstname.lastname@example.org www.hdsa.org
Huntington’s Disease Youth Organization HDYO PO Box 6371 Delray Beach FL 33482 Email: email@example.com https://en.hdyo.org
Hereditary Disease Foundation 3960 Broadway 6th Floor New York NY 10032 Phone: 212-928-2121 Fax: 212-928-2172 Email: firstname.lastname@example.org www.hdfoundation.org
Huntington Study Group (HSG) University of Rochester, HSG Administrative Office 1351 Mount Hope Avenue Suite 223 Rochester NY 14620 Phone: 800-487-7671 (toll-free) www.huntington-study-group.org
- Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA, Scahill RI, Wetzel R, Wild EJ, Tabrizi SJ. Huntington disease. Nat Rev Dis Primers. 2015;1:15005.
- Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA, Scahill RI, Wetzel R, Wild EJ, Tabrizi SJ. Huntington disease. Nat Rev Dis Primers. 2015;1:15005.
Brenna: You're listening to the Rare Disease Connection, a production of Aspect Health and raredisease.com. When someone is diagnosed with a rare disease, the effects of that diagnosis are not only in the patient, but their entire family. Today we're going to talk about a condition called Huntington's disease with roughly 41,000 symptomatic Americans and more than 200,000 at risk of inheriting this disease. A diagnosis of Huntington's disease is felt across entire families. For families facing a new diagnosis, you likely have more questions than answers and that's why we're here. The Rare Disease Connection and our additional resources on raredisease.com and yourdna.com brings together the people whose expertise can explain what you're facing. Brenna: From diagnosis to prognosis, to treatment options, all the way to questions like who do I talk to? Where are the people that have been through this before? You'll find those answers here. From doctors, geneticists, academics, genetic counselors, patient organizations, other patients and their families, they're all within your reach and we're here to connect you. This is the Rare Disease Connection. Brenna: Hey everyone, this is Brenna, cohost of the Rare Disease Connection and director of patient education yourdna.com. Today I'm going to bring you conversations with four experts on Huntington's disease. Before we get started, you should know that this podcast is just the beginning. We have taken the information from this podcast and added additional resources, explanations, links and references for you in a downloadable guide. You can get your free copy by going to rare disease.com/huntingtons. That's rare disease.com/huntingtons. So let's get started. Our first conversation is with Fallon Brewer, a certified genetic counselor in Birmingham, Alabama. Thanks so much for joining us today Fallon. So why don't you tell us just a little bit about yourself. Fallon Brewer: Sure. I received my training in genetic counseling at the university of Utah. I'm currently one of the lead genetic counselors at the University of Alabama Birmingham. And my involvement with the Huntington's disease community is primarily providing genetic counseling for individuals pursuing predictive testing for HD. Brenna: How long have you been involved with the Huntington's disease community? Fallon Brewer: About 10 years that I've been doing this. So quite a while now. Brenna: So it seems like you have a wealth of experience. So speaking to that experience as a genetic counselor, what immediately comes to your mind when you hear Huntington's disease? Fallon Brewer: That's a great question. I think there's so many things that come to mind. But I think one that stands out is hope. I believe that there is so much research and so many promising therapies and treatments that are being investigated, whereas previously management was largely symptom-based. I'm hopeful in the near future that the management will be more disease-based, meaning slowing disease progression and ultimately stopping disease manifestations. Brenna: I think that's something that probably everyone's looking forward to. So let's back up just a second. From my understanding, Huntington's is a genetic condition. So what's actually occurring genetically that causes Huntington's? Fallon Brewer: Right. So it is a genetic condition. And Huntington's disease is caused when there is an expanded trinucleotide repeat on only Huntington's allele. So it's specifically a CAG repeat. And we all, all individual have two copies of the Huntington's gene and when one of those copies is larger than it's supposed to be, or it gets expanded, the gene is unable to work properly, and that's what then causes the symptoms of the condition to be able to appear. Brenna: So let's say someone has this expanded allele. They have Huntington's disease. What's the risk for their family members to also have this condition? Fallon Brewer: Right. We get that question a lot and [inaudible 00:04:42] more dominant condition, which means that any individual who was born with HG, whether that person is symptomatic or not, has a 50% chance to pass the condition on. Brenna: So are you saying that some individuals who have this expanded allele are not going to be symptomatic? Fallon Brewer: Everyone with the expanded allele will develop symptoms at some point. But that would be a later onset, sometimes not until the forties or fifties or sixties, sometimes even later. And so sometimes people are already, have made their family planning decisions and had children well before knowing that they have this condition themselves. They're just not symptomatic. Even though it's something they were born with and had their whole life, it takes many decades in most cases for those symptoms to show up. Brenna: So how common is this condition? Are there certain populations that are more likely than others to have Huntington's? Fallon Brewer: Right. So Huntington's disease affects about three to seven per 100,000 people of European ancestry. So that is one of the more common populations. There are some in South America, like Venezuela for example, where the overall prevalence of HD is about one in 20,000, so more common. Even a particular area in Maracaibo which is in Venezuela, it's one of the most Northern Lake regions in that country has a much higher prevalence of about seven cases per 100 people. So there certainly are populations in which it is more common. And likewise, there are populations in which it's less common such as individuals of Japanese, Chinese or African descent. Brenna: So it seems to really vary by ethnicity. Does it tend to vary by gender or socioeconomic class or anything like that? Fallon Brewer: It does not. So men and women are equally affected with this condition. And the economic status does not influence that either. Brenna: I'm curious about how someone actually receives this diagnosis. Are there certain signs or symptoms that would make a physician or genetic counselor suspicious of Huntington's? Fallon Brewer: There certainly are. Some of the early signs and symptoms can include things like depression and irritability, poor coordination or trouble learning new information or making decisions. But it's important to know these early symptoms are very nonspecific and they can also be observed in people who do not have Huntington's disease. So these symptoms don't allow for a clinical diagnosis to be made. There certainly are more influential symptoms that are things like involuntary jerking or twitching. Those movements are also known as chorea. So sometimes you hear Huntington's disease referred to as Huntington's chorea, so there's involuntary movement. And that's actually one of the key symptoms in clinically diagnosing someone with this condition. But as the condition progresses, the movements become a lot more pronounced and individuals may have trouble walking, speaking, swallowing. But there certainly are signs and symptoms that we look for both genetic counselors as well as physicians and other healthcare members who see these patients. Brenna: So I know you're mentioning like a clinical diagnosis. How does someone actually receive that diagnosis? And is there something different than a clinical diagnosis? Fallon Brewer: There is. So a diagnosis of Huntington's disease can be made one of two ways, either clinically, which means based on symptoms that the person is exhibiting. And again, these need to be more of the motor or movement type symptoms that chorea that I was talking about earlier. But it's always good to confirm a diagnosis with genetic testing. So a molecular diagnosis. And a genetic diagnosis is performed by sending ideally a blood sample from the patient to a lab that offers testing for HD. And then that testing lab runs analysis to determine the number of CAG repeats for each of the individuals Huntington's alleles. So if one of those repeat numbers is 40 or more, that would confirm a diagnosis of HD. Brenna: So I know you were talking earlier about how the number of repeats maybe can indicate like when someone might be showing signs or symptoms. So what about someone who isn't showing signs or symptoms but has a parent who was diagnosed with Huntington's disease? If they want to know their status, how do they get those answers? Fallon Brewer: Exactly. So and that's largely what I deal with working with predictive patients in the HD clinic at UAB. There is a process put forth by the HDSA, which is the Huntington Disease Society of America. And that process allows for someone who is at risk based on family history, but they themselves are not showing any signs or symptoms. Then they go through this process or predictive testing protocol, which typically involves a genetic counseling consultation, a psychological evaluation, a neurologic exam, and then a blood draw ultimately for the testing to be done. And so while the steps may vary from center to center or place to place, that's kind of the model that's put forth by the HDSA that's recommended to follow. Brenna: So thinking about the flip side of that, maybe someone just got diagnosed and they're wanting to have a family, what sort of advice would you give for family planning? Fallon Brewer: Yeah, there definitely are options out there for individuals who may find themselves in that position and meeting with a genetic counselor or reproductive endocrinologist could definitely be helpful so that the person can be informed of each of their options and be able to make a fully informed decision that's best for them. Brenna: Now that we've spent time talking about what Huntington's disease is and how someone receives a diagnosis, what's your best advice for someone who is diagnosed with Huntington's or maybe who has a loved one who is diagnosed? Fallon Brewer: Sure. I think HD is a life changing diagnosis, not only for the person being diagnosed, but also for their loved ones and their caregivers. So my advice would be to really try to utilize the resources that are available to them, whether that be a centers of excellence where they are able to be followed by a multidisciplinary team of healthcare providers. Usually that includes neurology, social work, various therapies like physical or speech therapy, psychiatry and others to help manage the symptom usually with medication or altering home accommodations. But by utilizing the team, the family and the patient can be aware of clinical trials and research that they may also be eligible for. So that can definitely be helpful. Fallon Brewer: And I would also recommend trying to participate in a support group for HD. I think for some people feeling connected and being able to network with other families who are on a similar journey can be helpful. So if that's something they feel would be helpful for them, I definitely would recommend seeking out those groups, whether they be physically located near them or there's a lot of different options with technology now to participate in support groups. But most importantly, I would say, don't give up hope there. I said earlier, there's so much promising research being done that hopefully can provide a cure for HD one day. So say hopeful and take advantage of those resources. Brenna: So speaking of those support groups as well as centers of excellence, is there a place that you'd recommend for patients to go to get that information? Fallon Brewer: Yes. So the Huntington's Disease Society of America has a great website. It is hdsa.org. And on that website you can find a centers of excellence near you or if there's not one directly in your state, you can find which one may be closest. They also have a lot of other great resources, just patient information, booklets about the genetics of the condition, about different clinical trials and research being done and other ways to connect. So that website really has a lot of great information. And I think for those who are also trying to, due to reasons whether their insurance requires it or they prefer to go, if they're predictive and need to go through that process, they can also find a genetic counselor near them by going to nsgc.org. And there's a find a counselor button there that can help connect them with someone in their area that can get them plugged in and connected where they need to be. Brenna: Thanks Fallon for taking the time to talk to us today. Whether you've interacted with the genetic counselor yet or not, they play an invaluable role in the journey of anyone diagnosed with a rare genetic disease. If you think you or your family might have Huntington's disease, I would recommend looking at nsgc.com to find a genetic counselor near you. Our next conversation is with Hope Heller. She is a clinical social worker currently working as the clinical director of operations at Georgetown university's Huntington's Disease Care Education and Research Center. Thanks so much for talking to us today. Why don't we start out with you just telling us a little bit about yourself. Hope Heller: My name is Hope Heller. I'm a licensed clinical social worker in the DC Metro area. I have been a social worker for over 10 years now. I've always worked in healthcare. I finished my masters at University of Pennsylvania in 2008 and then I've been working with the Huntington's disease community for a little over 10 years now. I started out as the local chapter social worker doing support groups and resources and I worked at that for about six years. While I was doing that, we opened the first multidisciplinary Huntington's disease center in Washington DC at MedStar Georgetown University Hospital. So I've been at MedStar in the Huntington Center since it opened in 2012. Brenna: So thinking about that experience as a clinical social worker, what immediately comes to mind when you hear Huntington's disease? Hope Heller: I think about the families and the people as individuals. I can give you the laic scientific list of symptoms, but the truth is I think about a person in their family, if you have a parent with Huntington's disease, you have a 50% chance of inheriting it and you have to make all sorts of decisions with that as far as to get tested to not get tested. To me, I always think about there's the piece of the symptoms and the disease and then there's the people and the families and how much they're affected by it. Brenna: So thinking about the diagnosis of Huntington's disease, how does someone actually go about receiving a diagnosis? Hope Heller: Right. So there are two different pieces that I want to make the distinction of. So it's largely a clinical diagnosis and that is different from the gene tests. So just, I'll break it down. At the age of 18, so you're born with the genetic mutation, but once you are 18 you can go into a HD specialty center, go through the genetic testing process and find out if you have the gene mutation. So you can be gene positive and have the gene mutation, that is not a diagnosis. So I always like to make that distinction that just because you've been told you have the gene, you have not been diagnosed. The diagnosis is, it's clinical. So it's based on psychiatric components and motor symptoms. There's back and forth. And I'll be honest, I think it depends on probably what doctors you talk to now. Hope Heller: Typically, at this point we don't diagnose without a certain level of motor symptoms. Some of that is because some of the psychiatric components could be separate from Huntington's disease and that is harder sometimes to tease out. But so you would see an HD specialist or a neurologist or a neuropsychiatrist and they would look at your symptoms and look at your family history. And if you have a known family history, you can technically receive a clinical diagnosis without testing. Before 1993, there wasn't a gene test easily accessible. So people were diagnosed largely on family history and symptoms. Brenna: If they were to look at someone's brain of someone who has Huntington's disease, would there be differences to someone who does not have this condition? Hope Heller: So in the basal ganglia, you're going to start to see more atrophy. That being said, and I've asked the neurologists that I work with many times, it doesn't seem to always be something that's caught on brain imaging. And the explanation I've been given is that if somebody comes into a neurologist without a known family history and a lot of imaging is ordered, that I guess the view or the scan that gets used doesn't always look at the brain and that it's not a picture that's typically taken, if that makes sense. I'll defer that really to the experts. But yeah, you're going to start to see atrophy, especially in the basal ganglia. Brenna: So thinking about someone who might have just received a diagnosis or who might be concerned that they carry the Huntington's disease repeat, then if they were looking to start a family and we want him to make sure they didn't pass this genetic change onto their children, what sort of family planning options would a couple have? Hope Heller: So there's actually like a good variety of options and a lot of people don't know about them. And a lot of people just assume, well I have this gene so I guess I can't have kids. Or if I have kids, I have to put them at risk. So I want to just start before I give any options by saying that I feel very strongly that people should make their own decisions about family planning and that the choice to have kids or not have kids and how you do that is so personal. So we give our patients the options, but we really encourage them to talk to their partner, to talk to their family and really decide what works best for them. So the first option is to have kids the old fashioned way. Now that's not a way to not pass it along. If you just have kids the old fashioned way you have a 50% chance if you have the gene of passing along that gene mutation. There is something called PGD IVF and that is where you go through the process of doing in vitro fertilization. Hope Heller: And once you get to the stage where you have embryos, the embryos themselves are tested for the Huntington mutation. And then only the embryos that do not have the mutation are implanted. For some people it's a concern from religious standpoints and own views of what happens to those other embryos and all the things that go along with IVF. But that is sort of the best way in terms of having your own children with your own DNA with your partner that you're not passing along. I think the process can be 20 to $50,000 or more and it's variable what insurances cover, don't cover. I think most people end up paying largely out of pocket. I believe in the UK, if you do this, you get two rounds of IVF free through their health system, but in the US it ends up being largely out of pocket. Hope Heller: Then depending on if it's the male or the female that are the gene carrier, there's always a donation or sperm donation and then adoption also is an option. The other option is and this comes up is if somebody has largely planned to go through one of these processes or hasn't made a choice about whether or not they want kids because they don't want to pass it along and there is a pregnancy you can test in utero. Again, I am a firm believer that a woman should make her own choices about her body. I have no opinion one way or another about this piece, but the idea behind testing in utero is that if the fetus does test gene positive, then you would not continue that pregnancy. It happens. I think it probably happens more than people talk about and some people choose that option as opposed to other routes because it is less expensive. Hope Heller: But the one thing that I tend to say to people is if this is a child that you want, if you are actively trying to have a baby and this is how you're planning to rule out Huntington's disease, you have to think about how you're going to feel having to make that decision. I think it happens outside of HD where you find out something in a pregnancy and have to make a tough decision. But obviously going into it with HD, there's a 50% chance that that's the answer you're going to get. And we don't want somebody to test in utero, have a child that is gene positive, you know it's gene positive and then you continue that pregnancy. Obviously you can't force somebody to end a pregnancy. But the piece to that is we don't test until somebody is over the age of 18. There is rare cases of juvenile onset HD, but we consider it largely in adult onset disease and therefore we consider it an adult decision to get tested. Hope Heller: There's a lot of ramifications and there's a lot that comes with having that information. So it really becomes an ethical issue for a child to be tested, to know that they're gene positive growing up when they may not have an onset of the disease until their thirties, forties, fifties, sixties. So again, those are sort of the main options as far as having kids. And so what I always say to people is you have to think about what's going to work best for you and your family. But those are important conversations to have. How are we going to do this? How are we going to talk about Huntington's disease with our children? What are the resources? Hope Heller: I'll put a plug right in here for HDO, the Huntington's Disease Youth Organization. HDO really does a nice job talking about the importance of making sure that young people know about the disease and understand it and know what's going on. But those are all pieces that when you're talking about family planning, you want to look at not just how do I have a child and not pass the gene along, but then how do I still plan for the life of that child? And life happens and things happen and you can only plan what you can plan, but there are things to know and think about ahead of time a little bit. Brenna: So switching gears just a little bit, thinking about the signs and symptoms of this condition, what are some of the first signs and symptoms that might appear for an individual with Huntington's disease? Hope Heller: So the earlier symptoms tend to be largely cognitive or psychiatric and mood related. So it can sometimes be a little bit tough. Depression and anxiety can be early signs of Huntington's. That being said, it would be perfectly normal for somebody who knows that they are at risk for Huntington's disease or somebody that knows that they are gene positive to have depression and anxiety and it not be that first symptom. So I don't want anyone listening to this to be at risk and be like, "Oh no, I have depression and anxiety. I must be in the early stages." It's not. We really look to sort of personality changes and bigger mood changes. If somebody is suddenly more irritable than they used to be, has a shorter temper or suddenly becomes more empathetic, the depression and anxiety really start to sort of spiral out. Hope Heller: So I'll sort of back up for a second and say that regardless of the onset of Huntington's disease or not, the treatment for those early psychiatric symptoms are going to be the same as the general population. So the sooner seek treatment and manage those symptoms, you know the better quality of life we see especially in those early stages. We might also see somebody starting to have difficulty with their job or work or with executive functioning skills, paying the bills, keeping your schedule straight, becoming more forgetful about little things. I will also put an Asterix in that that I will get calls from young moms that are at risk or they're gene positive and find themselves more forgetful or having a harder time managing things. And I'm like, "Well, do you have kids?" And I'll get answers, "Oh, I have a two year old. I have a four year old. I have a one year old." Hope Heller: As a mom of small children, it's also perfectly normal because of those reasons to have some of those signs. So I say that not to talk people out of getting treatment or realizing that there's could be something wrong. I say that more so that somebody that's at risk or knows they're gene positive doesn't suddenly think, oh my goodness, I'm already showing signs. But those would be the earlier things. You would look to some balance issues if you're starting to fall, if suddenly riding a bike is harder. It's a relatively slow progressing disease depending on the general age of onset. So you're not going to see changes over like weeks to months, you're going to sort of see changes over months to years quite often. Those are sort of the early things. And again, that's why we always say, I always tell people really talk to the doctor early. We always tell our patients and tell families that reach out to us are people that reach out to us to sort of find out what testing and diagnosis and treatments all about. Always call us. Brenna: So moving forward, those are some of the early signs and symptoms. What are some things that we should look for as Huntington's disease progresses and about how fast does this condition progress? Hope Heller: So it's going to be different for everyone. Dr. Sholsen said to me once a long time ago that if you've seen one Huntington's patient, you've seen one Huntington's patient because everybody looks different. But they say the average is 10 to 15 to 25 years. So like I said, you're going to progress. It's more that you're going to notice it maybe months to two years the changes. Especially in those earlier stages, our patients, we don't see too much change over those early years. The movement's going to start to get worse generally, will be pronounced, you'll start to have more balance trouble, start to fall more. Mood symptoms may become more prevalent. They may become less manageable. I'm a really big proponent of psychiatric care in Huntington's disease because I think the difference of psychiatric care for the psychiatric symptoms is really night and day in your quality of life, in your interactions with your family. Hope Heller: The patients that come into us that have had this long history of psychiatric symptoms that haven't been managed, once I watch our psychiatrist who I in many ways think is a miracle worker, really manage those and get the ... because they can be managed with medication. But it's not an exact science. I think that what Huntington's disease psychiatrists do is an art form. Finding the right doses and the right combination of medications. But that difference between somebody that has come in with unmanaged psychiatric symptoms and when we get to that point that we found the right plan, it's just amazing. It's amazing for that patient. It's amazing for their family. I'll have conversations with families forever about how hard things are and I'm like, "Stick with us, I promise." And so I really stress that the psychiatric symptoms are things that I feel like HD specialists usually can manage. And over time they'll need to readjust those medications. Hope Heller: But so you'll see a change in the psychiatric symptoms over time. Sometimes as someone progresses, those do get a little bit better. Sometimes they can get worse. And there's always the concern with impulse control and depression about the risk of suicide and high rates at it because of that impulse control and not having that time to stop yourself, but you'll see cognitive symptoms. Somebody will eventually not be able to work anymore. We always encourage people to sort of figure out the right timing to talk to their work about reasonable accommodations and then going out into stability and what all of that timing looks like for each person. Eventually a person will not be able to drive. In my experience, the first hardest conversation that we have with a patient is the diagnosis. And sometimes the harder conversation is actually the you should not be driving anymore conversation. Hope Heller: And that is because you are slower to react to things. Judgment may be impaired because of the movements. You may be a little jerkier driving. There are lots of factors that play into it and oftentimes the person will say, "Well, I have my radio off. I'm very focused." And it's quite honestly, it's not about what you are doing while you drive. It's if a kid kicks the ball into the street, is your reaction time fast enough to slam your brakes? If another car cuts you off, is your reaction time? And then as we get to the later stages, we're going to start to see swallowing issues, which is going to lead to weight loss, risk of aspiration pneumonia, and then again as the movement increase or as you progress, you're going to be more likely to fall. Some patients are still walking towards the end with significant help, but usually a wheelchair at some point or become bed bound as the movement increased. And there are good medications that can help manage a lot of these symptoms. Hope Heller: It manages them, it does not fix them. They're still going to progress and then at some point the medicines aren't going to continue to be able to alleviate all of the symptoms, the swallowing. There are things early on that can be done to make eating safer. I'm a really big fan of physical therapists, occupational therapists, speech therapists, and all the things that they can do for our patients throughout the course of the disease. What I find is the earlier on that you put an intervention in place, it's less sort of extreme for that person. You sort of slowly make adjustments over time. And so that way you're not going from being completely independent to completely dependent overnight. Brenna: So thanks so much for spending time with us today. In closing, I was hoping you could provide us with some of the best advice that you would give for someone who's received a diagnosis or a family member who's received a diagnosis of Huntington's disease. Hope Heller: Well, so before you get that diagnosis, if you're talking about genetic testing, I want people to know that you should go to a specialty center. If you don't have one near you, you should reach out to one and see if they can refer you to someone in your area that you know about. I think the best outcomes with genetic testing in terms of how a person handles it or manages it come from the people that have had good genetic testing, good genetic counseling and resources up to the testing point. I think you should only get tested if you yourself feel strongly about it. And then I would make sure before you do that process that you understand how that impacts life insurance, longterm care insurance, health insurance, those are topics I could talk about all day long. I won't. And that you know what your supports are after that. Hope Heller: And then somebody that's just been diagnosed, whether it's pre symptomatically or whether you have the clinical symptoms already. What I would tell you is there's a lot of scary things on the internet. Google is not your friend and we don't have a treatment or a cure that's going to slow the progression or stop it at this point. But we have a lot of really good symptom management tools at this point. And there are a lot of really excellent doctors that can help. And also the research is really incredible. And that's one of the things that I've been so ... I love getting to know our families and it's an honor really to be brought into their world because you're not taking care of a patient, you're taking care of their whole family. It affects everyone, whether you've got the gene, whether you don't have the gene, whether you've married into that Huntington's family, everyone's affected by it in their own way and to really be trusted by people is such an honor. Hope Heller: But the HD teams out there, they're really wonderful. And I would encourage people to talk to them early, work with them early, get involved in the get involved in research if you want to. Again, the research is really awesome and I love what I get to do and work with the families. It's been so exciting and to see the research out there and to see where things are going and I think there's a good reason for people to be hopeful. Part of that and part of being ready when there is a treatment available is taking care of yourself and managing those early symptoms and not waiting to see a doctor. We would rather see our patients more often than less often, especially in those early days. I think sometimes those early stages, people will say, "I don't want to bother them or I'm not that sick." Hope Heller: Or quite honestly in the early stages, you often don't recognize those changes. But I would encourage people and their families to reach out because they think that's the biggest piece are patients that I think seem to have some of the better overall course. And this is anecdotal, it's not ... are the ones that are talking to us and talking to the doctor and they're trying to manage things as early as they can. But again, I think there's reason to be hopeful. And I think just because there's not a cure, doesn't mean there aren't a lot of things that we can't do to make your quality of life better. And families still don't talk about this disease and it's largely still a secret. But I encourage families to talk about it. Talk about if you do have it or if you're at risk for it, what do you want? What are your goals? Hope Heller: I'm a big fan of advanced directives and being in control of your own healthcare. But those are all things I could talk about all day. But again, I think it's seeking treatment and care and there's a lot of support and research out there and I think the HD community as a whole has worked really hard to try to build resources and support families. And if there are supports that you don't have that you think you need or if you want, if you think a center should be doing more for you, I encourage people to talk to your care teams about that. What do I need? what do you need and see what they can provide or what services. Brenna: Hope. Thanks again for taking the time to talk with us. If you or someone you know was recently diagnosed with Huntington's disease, it is important that you identify a team of doctors that you trust. There are currently 50 centers of excellence across the United States for Huntington's disease. You can go to Huntington's Disease Society of America to find a center near you. Our next guest is Dr. Victor Sung. Dr. Sung is an associate professor of neurology at the University of Alabama at Birmingham. He is also the director of UAB's Huntington's disease clinic. Thank you for taking the time to speak with us today. So why don't you start off telling us just a little bit about yourself and your involvement with the Huntington's disease community? Victor Sung: Sure. So my name is Victor Sung. I'm a neurologist and I did training in movement disorders. So I did a movement disorders fellowship. And then at the end of my fellowship, the opportunity came along for me to become involved with Huntington's disease. And I had learned about the disease during my fellowship, but I didn't know much more than that before I took over the clinic. And that was in 2011. And currently I'm the director of our Huntington's disease clinic here at the University of Alabama at Birmingham or UAB. And we are at UAB a center of excellence. So the Huntington's Disease Society of America or HDSA has centers of excellence scattered across the country. And so we are one of the level one centers of excellence in the HDSA center of excellence program. Victor Sung: I also am on the board of trustees for HDSA and then the chair elect for the board of trustees. And so I've been working in the Huntington's disease space since I guess 2011. I'm involved in clinical trials and it is a big part of what I do. I kind of backed into it, but I fell in love with the patients and the families and they're why I keep doing what I do every day. Brenna: Thinking about all of that experience as a neurologist and your involvement in clinical trials and all of your work, what immediately comes to mind when you hear Huntington's disease? Victor Sung: Yeah, I think for me, I've been doing it enough and working with patients and families. I think the thing that comes to mind for me is probably different than what comes to mind for a lot of other people. I think just kind of the lay understanding of the disease is that it's a difficult neurologic, genetic disease and that's kind of what people know about it. But for me, I think about it in a different way in the sense that yes, it is genetic and neurologic and degenerative, all those things are true about the disease. And because of the disease, it has in multiple impacts on patient's lives, from behavioral to motor function and those kinds of things. But I look at it in a different way in the sense that because of that, if we can make improvements in the patient's life, then it will ... even small improvements are magnified and can have a big improvement on the whole family's quality of life because this disease definitely impacts the whole family. Victor Sung: And so I kind of look at it that way. I've always embraced the family aspects of the disease and I really feel like when a patient comes in and joins our family at our clinic, that they're kind of joining a big family and we're all in it together. And then the HDSA mottos I think are very pertinent. One of their big motto is help for today, hope for tomorrow. And then another logo they have on a lot of their stuff is family is everything. And I think those two slogans really sum up what I really think about when I think about Huntington's disease. Brenna: So you're much more focused on the family and more of a holistic approach than necessarily looking at the disease and all of its components. Victor Sung: Yeah, I mean certainly when I give lectures to residents or medical students, I can explain the little components of it, but I take a much bigger, broader approach. And certainly when I think of the disease or when I see each patient in front of me, we try to take a step back and approach things at a bigger level. Brenna: Absolutely. So maybe taking that step back with you, talking a little bit about the history of the condition. How was Huntington's disease discovered? Victor Sung: Yeah, I mean, the story of Huntington's disease is so fascinating. When I think about the history of it and how it was discovered, it really goes back to Nancy Wexler. Nancy Wexler is a neuroscientist who has Huntington's disease in her family herself. And she was recently interviewed by the New York Times where for the first time she revealed that she has the gene and has the disease herself. But back in the eighties, before that was known, before anything was known about the disease, we did know that there was this entity that seemed to run in families and there were hallmark characteristics like chorea and other behavioral changes, but had not really been described. George Huntington after which the disease is named first described the disease, this pattern in the late 1800 and the familial aspect of it. But really we didn't know. This was all pre human genome project. Victor Sung: We didn't really know much about the disease at all. And then Nancy's work, she in the late eighties formed this US Venezuela collaboration project where there's a village in Venezuela called Maracaibo that has a high concentration of people with Huntington's disease. The incidence of Huntington's disease in that village is 50%. So every other person in this village has Huntington's disease. And that was recognized even back then. And so Nancy really spearheaded this project to send neurologists from the US down to Venezuela and they basically examined every person they could find and decided, does this patient have symptoms or not? And then drew their blood and sent it on dry ice to the NIH. And they collected over 4,000 blood samples, sent it all to the NIH. And with those greater than 4,000 blood samples, they were able to isolate the gene and sequence the gene. Victor Sung: It was the first full genome sequenced in humans and the technology that was used to sequence that was really pivotal in setting up the human genome project. It's really fascinating, the scientist who, the geneticist who worked on that, his name is Jim Cassella, he's still at Mass General. And to hear him talk about how he did that work is amazing. He invented linkage analysis, which we don't use a lot now for genetics, but was critical then. And he really describes it like back then we knew about DNA and we knew about that there were genes and genetic code, but we didn't have the human genome sequence and there wasn't really a place to start. And he describes trying to do the human genome project without linkage analysis, like trying to put together a 5,000 piece puzzle with no edge pieces. Victor Sung: And that's kind of what it was like and that's why it hadn't moved forward. But with the linkage analysis that they used to help with Huntington's gene sequencing, they were able to kind of frame the edge pieces in and that was the critical step to getting the human genome project to move forward. So a huge, huge step for all of human genetics and genetic diseases. But really all started with Huntington's disease. And I love that story. And it's such an interesting way that even though Huntington's disease is a relatively small and rare disease, it has this huge domino effects that have impacted really the world of genetic science. Brenna: So with your work at the clinic at UAB, I'm sure you are involved a lot with the treatment and care of patients who have Huntington's disease. So what are some of the treatment options for people with this condition? Victor Sung: Yeah, I think that's a common misconception that oh, it's genetically programmed degenerative disease and so it's so sad and there's nothing that can be done, but that's actually not true. There are two FDA approved drugs in the United States that will treat the motor symptoms of the chorea of the disease. And those are very effective treatments. There are other medicines that are used off label to treat the motor symptoms of the disease as well. And then the behavioral symptoms of the disease, while they're not FDA approved, I mean, the way I describe it is we have antidepressants, we have anti-anxiety agents, we have anti-psychotic agents. So if a Huntington's disease patient is having depression, anxiety or some of that psychotic features, those drugs can be used in Huntington's disease as well to treat those symptoms. Victor Sung: Those drugs, they all work in biochemical ways in the brain. And since there are structural and chemical changes in the brain caused by Huntington's disease, in some ways those behavioral symptoms are treated maybe even more effectively in Huntington's disease than they are say just with your person on the street who has depression. So those can be effective as well. We don't have as many treatments for the cognitive or the thinking and memory type symptoms of the disease, but we're working on those as well. And I still feel like if we can make an impact on the motor function, make swallowing better or walking better or balance better or coordination better. Those from a motor standpoint, that has a huge impact on the patient and the family's quality of life. And then if we can make the behavioral symptoms better, irritability or impulsivity or anger or aggression, depression, anxiety, any of those things are causing a big problem. If we make those better, that can have a huge impact on the patient and family as well. Brenna: Yeah. So just focusing on those areas over all. But being able to just improve one area can really help with the overall health of the patient and as well as quality of life. Victor Sung: Yeah. And that's a lot of things that can be impacted in a patient's quality of life by the disease. And if you read about it, it seems really daunting. But I find that most patients don't have all of those all at one time. It's not like a patient is going to have swallowing problems and walking problems and coordination problems and severe depression and severe anxiety and severe behavioral problems all at the same time. It doesn't really do that. It kind of comes and goes. Each person's a little bit different. Month to month it's going to be a little bit different and we focus on what the problem is right now. We work on that, get that better. And then keep going as things go along. Brenna: So with all of your work, is there a cure for Huntington's disease? Victor Sung: Well, there currently is no cure for Huntington's disease. But it depends on, I'm a glass half full kind of person. So that's how I look at it. We don't talk about the common cold as an incurable disease of the nose, even though we could. I mean there's so many things in medicine that we don't have a cure for. Plus, while we don't have a cure yet for Huntington's disease, we are getting ever closer. Right? So we have, I mean this mantra that HDSA has, which is help for today hope for tomorrow is definitely true. We have symptomatic treatments that can help today and then we're building from a scientific standpoint, things towards a cure that is really hope for tomorrow. And because of the genetic aspects of the disease, I have patients with other diseases like Alzheimer's or Parkinson's disease that have a lot more public notoriety I guess, and certainly a lot more people have those diseases. Victor Sung: But take those diseases as examples, we don't have a good handle on what the exact cause of Parkinson's disease is or what the exact cause of Alzheimer's disease is. And when you don't have that, it's hard to target a disease and cure it, right? But for Huntington's disease, we know what the cause is. The cause is that mutated gene and all the things that come out of it. So it's as simple and as complex as stopping that mutated gene from doing what it wants to do. And it's funny, back in the early nineties when the gene was finally sequenced, the gene was sequenced in 1993. A lot of people felt like back then, oh, well, within five or 10 years we're going to have a cure for Huntington's disease. And it's proved a lot harder than that. Victor Sung: But finally, now the last five years, really things have really picked up and our sciences to the point that we can do the things now that we had only dreamed about doing back in the nineties. So there are multiple disease modifying or curative type strategies in investigation in human beings right now. So that's really exciting. We're closer than we've ever been. And I think yes there are exciting things that everyone wants to talk about like CRISPR and things like that. Those are still in animal models are mouse models. So to me that's still far away. I mean, I'd love for CRISPR to be a reality, but the real truth is that that's further away for humans with Huntington's disease. But we have other technologies that are in investigation in human beings with Huntington's disease right now. One of them is in a phase three trial, which is the last step that you need before FDA approval. So that's as close as you can be. So all those things are really exciting. Brenna: So I understand that UAB is a test site for some of this new research that you've been talking about. Can you tell me a little bit about some of the drugs and treatments that are being developed currently? Victor Sung: Sure. I mean the one that I was referring to that's in phase three trials is they just released it publicly that it has a drug name now. It's called tominersen. And it's being studied by the drug company, Roche Pharmaceuticals. We are a site for that phase three trial here at UAB. Obviously as a participating site, we are blinded, the patients are blinded. So I have no idea what my patients are getting and the patients don't either. And we are just one site of many sites globally. So I certainly don't have any sense of is it going to work or not, but we have to do the work to do it. The way that the drug works is it's an antisense oligonucleotides or an ASO which we introduce via lumbar puncture so that it gets from the spinal fluid, then that spinal fluid feeds the brain, and then the drug gets into the brain in that kind of way. Victor Sung: And then the drug will get into the cells in the brain and slow the production of mutant Huntington protein in that kind of way. So that's the exciting thing about it. The thing that's been published from the phase two trials for tominersen is that patients who received the drug in the phase two trial averaged a 40% lowering in their circulating meat and Huntington protein in the spinal fluid. So that's pretty effective. The phase three trial now is to show, well what does that mean clinically and does that mean that we're clinically achieving disease slowing or complete arrest of the progression of the disease? Or are we just slowing the progression of the disease and what does that really mean for the clinical status of a patient. Victor Sung: But I think that's really promising that it's doing what it is trying to do, which is lowering the levels of the main Huntington protein. So that's probably the most exciting because it's the closest to reality. But there are other technologies under investigation as well using other gene based. There's RNA interference that's being investigated. There is an allele specific antisense oligonucleotides being investigated that's in phase two trials. So we have multiple other technologies that are in phase two trials and then this big one and the phase three trial. It's really interesting. I think on this side of it doing the work. I've, like I said, been doing this since 2011, but there are certainly people in the field who have devoted their entire careers, their entire lives to the study of Huntington's disease and they've worked for 20, 30 years. And to finally see these kinds of disease modifying therapies getting close to come to fruition, I can't imagine. I mean, it's exciting for me, but I can't imagine what it's like for these other investigators who have devoted their entire careers to it. Victor Sung: And one of the interesting things that Roche has said for this phase three trial is that Roche as a company was founded in the 1920. So it's a big, very, very old pharmaceutical company that's global and this big phase three trial for Huntington's disease when it launched, they filled 600 slots for the trial, for the phase three trial in 30 days globally. And they said that, Roche said that in the entire history of their company since 1920, this was their fastest enrolling phase three trial that they have ever done in any disease period, which is stunning and amazing in a lot of ways. I think that speaks to how engaged and dynamic the patient and family population is in Huntington's disease. Victor Sung: If you talk to any clinician and researcher who works with Huntington's disease, they'll tell you the same thing is that we are inspired by how our patients and families rise up and meet the challenge that is here every day. And they've shown that. And that's another example of that is they all were ready to participate and ready to go so that we didn't have to go looking for patients. They came to find us and they wanted to participate and get this trial going. So obviously our research community is pretty activated too. We had to be ready to receive all of those 600 patients globally. So there's that too. But I really think it speaks to the dynamic community, both patients, families, clinicians, everybody that really surrounds Huntington's disease and makes what we do so interesting and so rewarding. Brenna: I can definitely hear the passion and excitement, engagement and hope as well in your story and hearing about this trial. Victor Sung: It's exciting. I have to temper my excitement. Obviously I'm a very enthusiastic, exciting person and that's a temperate a little bit and we have to do the work and we have to do the science and do it the right way. But it feels like I mean I can just tell you like the energy in the room at all of our big Huntington's disease research meetings is, there is an electric energy in the room because people can feel it. It's like when you're getting close to something, you're approaching that finish line, that extra adrenaline burst that you get so you can finish the race strong. I think people can feel it and that's exciting. Brenna: My final question of today is what is your best advice for someone who's been recently diagnosed with Huntington's disease or who has a loved one who's diagnosed? Victor Sung: I think my biggest advice has been the theme of what we've talked about today, which is don't lose hope. It's not the end, it's the beginning of a journey with a new diagnosis and there are lots of resources out there. Reach out to the community. The community will embrace you. The Huntington's disease community from a support standpoint has a really strong online presence from online support groups to Facebook groups and all these kinds of things. So reach out to the community and you'll really be embraced and they'll help you to get plugged in and then get plugged into the resources that you have locally. Between all of the clinical and research organizations for Huntington's disease, there is a reach that covers really most of the United States and really most of the world. So just reach out and find and connect with a center, whether it's a research center or a clinical center, there are people there who can help you. Victor Sung: And then if you want to be a part of the research towards a cure, there are opportunities to participate. Obviously the Roche trial is full now, the phase three trial, but as I mentioned, there are multiple phase two trials ongoing that hopefully if they're successful will go to phase three in the coming years too. So there's stuff's coming very soon. So there's lots of opportunities to get involved and lots of opportunities to get help to deal with everything that you're going through now and in the future too. I think most of us that do it are in it for the long haul. So just this message that you're not alone and there's tons of websites and we can list them later or list them at the end here. That's where people can find resources where they can get help and get questions answered. Brenna: Thank you Dr. Sung for your insight. It's clear that while there's not currently a cure for Huntington's disease, there's definitely a reason to have hope for the future. Our final guest is Tyler Oram. Tyler is a medical student at the university of Alabama at Birmingham, who is involved in creating awareness about Huntington's disease through the organization of a Team Hope walk each year in Birmingham. He also has a personal connection to this condition. Thanks so much for joining us today. So why don't you just start by introducing yourself, telling us a little bit about you. Tyler Oram: Okay, so I'm Tyler Oram. I'm a third year medical student in Birmingham, Alabama. I'm originally from the Mobile area and came to UAB several years ago to study neuroscience as an undergraduate. Currently I serve as a director for the Birmingham Team Hope walk, a charity walk that raises money for the Huntington's Disease Society of America. And last year I was also involved in research examining the cost of pre-symptomatic tests for Huntington's disease at HDSA centers of excellence across the country. But my path to where I am now began with my dad being diagnosed with Huntington's disease when I was a teenager. Brenna: So speaking from your experience as someone who's had a family member with Huntington's disease, what immediately comes to your mind when you hear Huntington's disease? Tyler Oram: I sort of start to feel pain and fear. HD is such a tragic disease because you feel helpless as you watch it progress in your loved one. And as it was in my case, my father. And in the case of mine and many others, you also have a lot of fear because you're worried about going through the exact same thing later in life. Brenna: So that seems like a lot to handle. Tyler Oram: Yeah, it can be a lot. I mean, obviously having Huntington's disease is awful, but it can really take a toll on an entire family as everyone kind of watches and for children to kind of fear for their own future. It could be a lot of different kinds of emotions to try and take in at once. Brenna: Yeah. So let's back up a little bit. Why don't you tell us a little bit about your dad maybe before diagnosis and then after. Tyler Oram: Yeah. So my father was a kind, hardworking man that grew up in Mobile and lived there all his life. He was very active too. He loved water skiing when he was younger. And he worked at the same company in Mobile for over 30 years. And I think the madness that I ever saw him was when he found out that he wasn't going to be able to work anymore. Within a couple of years after his diagnosis with HD, he couldn't work anymore. He wasn't able to drive and he really struggled with the freedoms that he lost. He was kind of confined to just being at home all day and there really wasn't that much he could do and it really took a toll on him emotionally. He became a lot more irritable. Honestly, he was kind of at times hard to be around him because he was just so all the time. It just kind of spread to the rest of our family. It was a very difficult experience. Brenna: So as you mentioned a lot of times with HD and it was echoed by other people that we've heard from today, it really does take a toll on the whole family. And so you've spoken about a little bit about like the anger and maybe that it was difficult to be around him, but how else did your family react to this diagnosis and in everything that you guys went through? Tyler Oram: I mean, when we first got the diagnosis, it was a little bit before my father and my mother first told me and my sister. And when we got the diagnosis or when my sister and I were told, I didn't really know what to make of it. I was in eighth or ninth grade at the time and I didn't know anything about Huntington's disease. And so they told me this disease, there's no treatment for it, there's no cure, but it's very slow moving. My dad told me that he would probably live up to another 20 years. So I knew it was bad, but I didn't take it as the end of the world. I think my sister took it pretty hard because she had more awareness than I did about what Huntington's disease was. So it wasn't much of a shock for me, but it was just more out of my just lack of knowledge about the disease. Tyler Oram: And right after his diagnosis, I mean I think we were doing pretty well. His symptoms weren't very severe, so it wasn't that much of a change from our normal lives. But as his symptoms progressed, it became a lot more difficult. Like I said, he became very irritable and he was home all the time, so we were always around it. But at the same time, you want to try and spend as much time as with some of that's sick as you can enjoy all the time you have left together. But so there's just a lot of things at play and it's a lot to try and balance. With him not being happy, having to stay at home all the time, but trying to find ways to still enjoy your time with him, it was just, it was difficult. Brenna: Yeah, absolutely. So you mentioned that you were only about eighth, ninth grade when you found out. Now looking at all of your training and all of your work with Team Hope and whatnot, if you could go back in time what's something that you wish you knew about Huntington's disease that might've been helpful for you or your dad or your family as a whole? Tyler Oram: I wish I had known more about how HD affects more than just movement. I think a lot of people get caught up in the movement, the chorea associated with Huntington's disease, but there's a lot more to it than that. HD also causes cognitive decline leading to problems with memory and planning for example. And it can also manifest with psychiatric symptoms such as depression, anxiety, and an increased frequency of suicidal thoughts. Suicide is actually a common cause of death in HD patients. There's just a lot more to the disease than I realized when my father first told me about it and I just didn't understand as a kid everything that my father was going through. Brenna: So it looks like you've taken a lot of your past and channeled it into what you want to do with your future. So studying neuroscience, going to medical school, but maybe most notably some of your work with the Huntington's Disease Society of America specifically you mentioned with Team Hope. So what can you tell us a little bit about Huntington's Disease Society of America as well as your work with Team Hope? Tyler Oram: Okay. So HDSA was founded in 1967 by Marjorie Guthrie. Her husband was the legendary musician Woody Guthrie who passed away that same year from complications from Huntington's disease. And so Marjorie devoted her life to searching for answers about the disease and she of course founded the Huntington's Disease Society of America. The mission of HDSA is to improve the lives of everyone affected by HD and they have a simple vision, a world free of Huntington's disease. And so HD is accomplishing their mission through several different ways from working with centers of excellence to provide clinical care to HD patients, to funding research for HD treatments, providing support groups for those affected by HD and so much more. Tyler Oram: One way HDS say raises funds is their events called Team Hope walks. Charity walks in cities across the country where each participant raises as much money as they can through donations from friends and family. So Birmingham has had a walk for the past four years now and we've raised over $40,000 in that time. This year we're having a virtual walk on May 17th due to COVID-19. It was originally scheduled for there actually, the first weekend in April, but we had to move it this year. Brenna: How can someone who might be interested and get that information once you guys know the details? Tyler Oram: Yeah. So one way you can check for our Team Hope walk and any events that might be in your area are to go through HDSA's website. There you can search for any events in your area such as Team Hope walks and there's a lot of other great fundraisers that HDSA hosts throughout the year all across the country. So HDSA's website, which is hdsa.org is the best place to find any events that are going on in your area. Brenna: Just in closing, wrapping up with your final thoughts. What's one thing or a couple of things, if Tyler Oram: I wish everyone knew how close we were to being able to treat Huntington's disease effectively. I think a lot of people affected by HD feel hopeless and that a lot of medical professionals, even ones that I've spoken with personally, see HD patients as lost causes. But we're so close to having treatments that stop or slow progression of the disease. With many diseases, we don't know the exact mechanism by which the disease develops. And this makes it very difficult to design treatments. But with HD there's a clear target and that's the mutant Huntington protein. It's this one specific mutation that causes HD. So if you're somehow able to lower the levels of this protein, you should see changes in how the disease progresses. And one such drug is already in a phase three clinical trial and has been shown to lower the mutant Huntington protein level in earlier trials. Tyler Oram: And there array of other drugs going through trials as well that are designed to stop that protein from forming. And the physician that runs the center of excellence at UAB, Dr. Victor Sung likes to tell everyone that we're going to have a treatment for Huntington's disease before we do for the common cold. And he's right. We're so close to having a treatment now that I think everyone should feel very encouraged. If you're at risk for HD or if you have HD, you should be very good about your future. Brenna: Tyler, thank you for sharing your story with us. If you're interested in getting more involved, please visit at the Huntington's Disease Society of America's website to learn more about opportunities to connect with the community. In closing, we've had the chance to talk to four experts today on Huntington's disease, but that's only just the beginning. We have taken all of today's information and included it in a free downloadable guide. You can get your free copy by going to raredisease.com/huntingtons. We would love to connect with you if you need to talk to someone, we're standing by. Go to raredisease.com/help. We're waiting for you. Rare Disease Connection is a production of Aspect Health and raredisease.com. Thanks for joining us.