Jessica: You're listening to the Rare Disease Connection, a production of aspecthealthandraredisease.com. There are roughly 7,000 rare diseases and estimates are that a rare disease affects nearly one in 10 Americans and hundreds of millions of people worldwide. When you hear numbers like that, it's clear that rare diseases aren't so rare and it's impossible to know how many rare diseases go undiagnosed. Jessica: The genetic disorder we cover in this episode is called neurofibromatosis type 2 or NF2. If you or someone you love is affected by a rare disease, you likely have more questions than answers. That's why we're here. 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, from diagnosis to prognosis, to treatment options, all the way to questions like, "Who do I talk to? Where are the people who've been through this before?" You'll find those answers here. From doctors, geneticists, academics, genetic counselors, patient organizations, other patients and their families all within your reach, we're here to connect you. This is rare disease connection. Jessica: Hi, everyone. This is Jessica, Genetic Counselor and co-host of Rare Disease Connection. I'm excited to bring you some recent conversations we've had with experts from around the world about a very specific rare genetic disorder, neurofibromatosis type 2. Before you listen, we know that hearing from these experts is only the beginning for you. That's why we've taken the information here and added additional resources, explanations, links and references for you in a downloadable guide on NF2. You can get your free copy of that guide by going to raredisease.com/NF2, that's raredisease.com/NF2. Head there for so much more to help you on your journey in understanding this disorder. It will certainly help support you and your ongoing plan of action. The experts are here so let's talk about NF2. Our first conversation is with Dr. Oliver Adunka. Let's hear from Dr. Adunka. Dr. Oliver Adunka: I'm an otolaryngologist. I do specialize, however, in what we call Neurotology. It's a relatively small field, which deals with disorders of the ear, so ear, hearing, balance and adjacent brain and that's why the NF2 topic comes in. Dr. Oliver Adunka: So, I grew up in Vienna, Austria and subsequently trained in Frankfurt, Germany, and always wanted to be a neurotologist, which is something that in that part of the world just wasn't available, so that's why I ultimately came to United States trained at UNC, stayed on there, and ultimately ended up at Ohio State in Columbus, Ohio. So, that's where I practice now. I have both an adult practice as well as a pediatric practice, so I practice at Ohio State at their hospital as well as at Nationwide Children's Hospital, which is the affiliated academic Hospital of Ohio State, so very large tertiary care practices. And that's really what lends itself to dealing with folks who have NF2. Jessica: Wonderful. We're happy to have you. And it sounds like you always wanted to be in this field, and is that really what got you involved with the NF2 population? Dr. Oliver Adunka: Yeah. So obviously, NF2 is a disease that allows us to really use our skills and our intimate knowledge with hearing balance and those cranial nerves that are involved, but really how I got involved is when I moved to Ohio State, I basically was hired as a replacement for another doctor who had research interest in it, too. So when I came here about six years ago, I pretty much took over this practice of many folks who have NF2 and they even told me, "Oh, you've got big shoes to fill." Dr. Oliver Adunka: So, slowly, I've become more familiar with NF2, the very specific management algorithm that's involved. All the other providers that you have to interact with, which is absolutely critical. And it became, I just had a much higher volume of NF2 patients than previously, right? Jessica: Great. And can you explain to our listeners what NF2 is? Dr. Oliver Adunka: Yeah, so NF2 is typically a hereditary disorder. It's called neurofibromatosis type 2. It should not be confused with neurofibromatosis type one, which is very different. Neurofibromatosis is usually something that causes benign central nervous system tumors, so brain tumors, mostly acoustic tumors. We call them vestibular schwannomas, but also meningiomas or ependymomas or benign tumors of the spine mostly. Again, it's a genetic condition. It's either inherited or it can arise from new, we call those the novel mutations. If it's inherited, it's usually autosomal dominant. Meaning that if you have NF2, there's a 50% chance of passing it onto your children, but again, 50% of the cases are new cases where there's no family history. Jessica: Then how common is NF2? Dr. Oliver Adunka: So, it's actually quite rare and it's interesting. The published literature and the numbers that are in the published literature are quite discrepant. It's from one in 25,000 to one in 60,000 people are diagnosed with NF2. Jessica: And what is the typical age of onset of NF2s? Dr. Oliver Adunka: Yeah, it's a good question, really. There are two main subtypes of NF2. One is called the Wishart type. It's a more aggressive version of NF2, where folks are diagnosed with brain, with those acoustic tumors or congenital cataracts, et cetera early on in childhood, typically in the second decade, so teenage years. That being said, however, we have several 7, 8, 9 year olds who are first diagnosed with NF2. There's another less aggressive type, it's called the Feiling-Gardner type. It's typically associated with a less severe genetic alteration and it's a less aggressive type. Typically, folks are diagnosed in their 20s and 30s, and have fewer tumors that grow less aggressively, too. So it's very critical for us to distinguish those two types, since we do manage them quite, well, somewhat differently, I would say. Jessica: And what does the long term outcome look like for those two types? Dr. Oliver Adunka: So obviously, with the Wishart type with a more aggressive version, it's more rapid progression, it's just more tumors. I think the tumor burden overall is much greater. Again, the tumors themselves, some more aggressive and oftentimes we see multiple tumors that sort of touch each other, that collides. We would not see that with the Feiling-Gardner type, which is less aggressive. So, overall with Wishart type NF2 patients, we do expect a more rapid progression of the disease and disability that's associated with that. Jessica: What is the underlying cause of NF2? Dr. Oliver Adunka: So, it's usually a specific gene on chromosome 22. It's a specific mutation. Several specific mutations have been identified, and again, the Wishart type has been associated with different type of genetic changes or what we call mutations than the Feiling-Gardner type, so the less aggressive type. But again, several mutations have been described on this chromosome, but again, it's on chromosome 22 and it doesn't code for a protein, it's called Merlin, and that acts as a tumor suppressor gene. So basically, if that's not working, well then those tumors, it's just a greatest statistical chance for those tumors to occur. Jessica: And how is NF2 typically diagnosed initially? Dr. Oliver Adunka: Yeah. So, if there's a family history, so there are familial types that are inherited, we usually have multiple options either the parent, one parent who is was affected will ask for either genetic testing or an MRI. And sometimes, we have diagnosed children with a more aggressive type, the occurrence of cataracts, which will be unusual obviously in young children. So, that's for the inherited part, where you sort of have this family history but again, genetic testing is available and you can basically sequence that entire gene and find out what specific mutation you're dealing with. Dr. Oliver Adunka: Now, for the spontaneous cases, again, sporadic cases happening in about 50% of the time where it's a new mutation, again, that the new mutation, then typically, symptoms will usually be the driving force, meaning asymmetric hearing loss, right? It's a very critical one that we usually get MRIs for asymmetric hearing loss to specifically capture whether or not there is an acoustic tumor or vestibular schwannoma present. So for all ENTs, basically, if folks see an asymmetric hearing loss then we're concerned about a vestibular schwannoma. Of course, in very young folks, if there's one vestibular schwannoma, we would look for a second one on follow-up MRIs, just to make sure. Dr. Oliver Adunka: Sometimes, however, we see other locations for tumors that cause various types of symptoms that we then follow-up with an MRI and on the MRI, if we see multiple schwannomas or meningiomas, then we would proceed with genetic testing to really map this all out and diagnose it properly. So usually, the MRI is somewhat critical in all of this. Jessica: And what does it appointment look like for someone who is newly diagnosed in your clinic and is there anything unique about your clinic that you wanted to share? Dr. Oliver Adunka: Yeah. So, I think the most critical part for NF2 patients is to have a team of doctors and not just one physician present, so we really have a team that is multidisciplinary, right? We often say we try to make it a one-stop shop and there's certainly a Catch-22 between how many appointments can you really have in one day, but not completely be exhausted at the end of the day, but we usually try Neurosurgery and myself, so Neurotology, Neurosurgery. Usually, we also have a neuro-oncologist as part of this team and then Audiology for hearing testing, so it's a lot of these tumors cause hearing loss and genetics, right? I think those are just the core of that team. Dr. Oliver Adunka: Of course, imaging is important, so oftentimes, imaging is part of that. Since we often image the entire neural access, meaning that we image MRI of the lumbar, thoracic, cervical spine as well as the brain, those MRIs can take three to four hours. So, oftentimes we have to break that up into multiple days. Other people on the team would be Physical Therapy and there's some additional electrophysiologic testing where we consult. A lot of already audiologists have that expertise, but that's important as well. So I think overall, big team, most is the front of the team, making sure that providers talk to each other. There's maybe even a conference set up, so I think that's absolutely critical. Jessica: And how often are patients typically coming to clinic? Dr. Oliver Adunka: So, it depends on the amount of symptoms and the size of the tumors. As a rule of thumb, I would say, we usually try to get neuro imaging once a year, sometimes with a document instability of some of these tumors, especially in the spine, we may defer spinal imaging for a year or so, so we'll obtain that every other year. But typically speaking, we try to get neuro imaging, again, of the entire neural axis once a year. Dr. Oliver Adunka: If there's a documented hearing loss, we would probably see patients more commonly, more frequently, just to get hearing testing done more often and with balance concerns then of course, so really, I would say that the symptoms really drive the frequency for the most part, but at least once a year, we would like to get MRIs. Jessica: Is there ever an opportunity for patients who don't have access to this multidisciplinary team for people like you to video conference or collaborate with their local physicians? Do you have any recommendations for that? Dr. Oliver Adunka: So, I think those are all great points and obviously, with the current pandemic, those Telehealth options have gotten a new value and actually, I would argue, we as providers continue to value them more and more, so I do think the future will be the inclusion of Telehealth in these decisions, right? Oftentimes, of course, the careful neurological examination is important, so I don't think it's possible to completely replace all the visits with Telehealth, but obviously, if it's easier for patients to obtain the MRI scans closer to home, then the films can be either sent with the discs, but right now, we can actually just share those over the web. So I think those are all very good options and we try to make use of them more and more. And the other thing that's hard to obtain via Telehealth type visits is, of course, hearing testing. Jessica: Right. What are the current treatments available to patients with NF2? Dr. Oliver Adunka: Yeah. So, there are multiple options obviously on the table. A lot of times we manage NF2 by just watching, right? So usually we're less, let's say, aggressive with managing these tumors in NF2 patients. However, sometimes, of course, with size and rapid growth, our hands are tied and we have to still operate on some of these, right? So, surgical management is really still a mainstay of management of NF2. It's often very complex, especially dealing with the associated cranial nerve deficits and dealing with hearing loss in particular, can be very complex in NF2 patients, so I think a good decision is always extraordinarily critical, so that's why the team really comes in, so I think the decision for surgery should be a multidisciplinary one. Dr. Oliver Adunka: And, again, Neurosurgery, Neurotology are absolutely critical in this and central. One can make careful decision on whether or not someone actually has surgery, and of course, surgeries very difficult to NF2 patients because the tumors that can be multiple tumors that basically touch each other. So, we just have to be very careful with surgery and the decision to do the surgery, and also recognizing that surgery is more difficult in sporadic tumors that are not associated with NF2. But that being said, surgery is still a main option for folks who have NF2 Dr. Oliver Adunka: Third option would be a hearing restoration, which can be done via multiple aspect, either multiple options. So, one would be just conventional hearing aids. The second option would be a cochlear implant, so despite the fact that these tumors sit on the acoustic nerve or close to it, we can still get away with cochlear implants to restore hearing when it's really as a moderate to severe hearing loss or substantial levels of hearing loss. We could rehabilitate with cochlear implants. So that's, I think, a good option for some folks who have NF2. Dr. Oliver Adunka: The third option, which really for us is something we don't like to resort to but oftentimes we have to, is an auditory brainstem implant. It's commonly referred to as an ABI and those ABIs are again, brainstem implants, those are cochlear implant-type hearing implants, that instead of placing them in the cochlea, we place them on the brainstem on the cochlear nucleus, so basically medial to those tumors. And this way, we can cause auditory stimulation so folks can still hear, not as well as with cochlear implants and hearing aids obviously, but it does enhance lip reading and so, it's a help. Jessica: Those are interesting treatments. Dr. Oliver Adunka: And the ABI is a device that was specifically developed for NF2. Jessica: Fascinating. Dr. Oliver Adunka: Yeah. So and then on another option for NF2, that's the more recent one really is and some of those are clinical trials, some of them are not, but Avastin is a breast cancer drug primarily, all right, so it's basically a medication that can be taken orally, so it's a pill basically, that can be taken to stabilize tumors in NF2. So it's predominantly used for folks who have an acoustic tumor, really two acoustic tumors and who start to lose hearing. It's really meant to stabilize the hearing loss, right? So, Avastin is form of the chemotherapy that we use. Obviously very different than traditional chemotherapies, but a good option for some folks with NF2. Dr. Oliver Adunka: There are some clinical trials that are also basically focused on oral medications, again, medications that can be taken in a pill form that are used to stabilize or shrink tumors. Some patients have tumors that respond quite well to them, but some patients are not. So, it's really it's quite unpredictable at this point and as we continue to use this drug in clinical trials, we continue to learn more about it, but that's certainly a probably a future option. Dr. Oliver Adunka: What we have hopes for, for folks with NF2 is gene therapy, right? I'm not an expert in gene therapy, but it's conceivable that we can inject some tumors, so we would still have to open them up and inject some substances in the tumors that could then shrink tumors. So obviously, that would be something that down the road we're very interested in learning how that would work, and how that would help our patients. Jessica: And as far as clinical trials that are ongoing, is there a way for patients to find out how they could be enrolled in this or is there anything going on at The Ohio State University or at your medical centers that they might be able to find out more about? Dr. Oliver Adunka: Yeah, so yes, we do have clinical trials at Ohio State and some of the other bigger centers across the country do have clinical trials. There are several sites that are good for patients to find out about. One is just to clinicaltrials.gov, so it's a government website. It's where every clinical trial has to be registered, so you can just search for neurofibromatosis type 2. So, there are not a lot across the country, but there's some, so it's certainly worthwhile looking into that. The website has several good information on what kind of what kind of indication, criteria there and what patients would be potentially candidates for this, so I think some of this information is really online. Jessica: Okay, great. And what do you think are the greatest barriers you see with patients with NF2 and then on the other side of that, what are your hopes for the future for NF2? Dr. Oliver Adunka: So, the barriers are that we don't have great treatments for NF2, right? We'd like to avoid surgery, but it's still one of the mainstays of treatment is we do these surgeries, they the risk for cranial nerves, such as the facial nerve, some facial nerve paralysis would be a problem that we sometimes see in folks have NF2, right? So, overall, the biggest barrier is that we need better treatments with the hopes for the future for NF2 is that really better hearing and plans for one, I would say, a better brainstem implant. We wish that it would work better, but also gene therapy and other therapeutics, medications really that we can administer to our patients or we could the patient administer it themselves that would really stabilize tumors, slow the burden of the disease or really just arrest this and also preserve cranial nerve functions such as hearing. So I think, those are really my hopes that we can continue to find ways to slow the growth of these tumors. Jessica: Thanks to Dr. Adunka. Jessica: Our next guest is Lauren Hanrahan. Lauren has NF2 and is an ambassador for NF2 BioSolutions. Thanks for joining us, Lauren. Would you mind sharing a bit about yourself? Lauren Haranhan: Sure. My name is Lauren Hanrahan and I'm 33 years old and I live in Florida. I am a wife, a mother to two beautiful children and a third grade teacher. Jessica: So, Lauren, would you mind telling us how you started your journey with NF2, neurofibromatosis type2 in your life? Lauren Haranhan: So, when I was 31 years old, during my second pregnancy, I noticed that I was having trouble hearing out of my left ear and I thought that I was just having a common earache and I went to my doctor and they looked in my ear and everything looked okay. She suggested that if the problem still was going on after my pregnancy to go see my ENT. So, after my son was born in September, that October, I had an appointment with my ENT and after doing hearing tests and MRIs, I was diagnosed with NF2 because they found a tumor in my left ear, which was causing hearing loss, and then they also found the bilateral tumor on my right side as well, so that was an instant indicator of being diagnosed with NF2. Lauren Haranhan: So then from there, I had to have a full body scan where they also came across three tumors located on each part of my spine. However, they're teeny tiny, so they have not caused any problems at that time. And so, after going to NF2 clinics and speaking with genetic counselor, it was 100% diagnosed with NF2 at that time. Jessica: And can you tell us a little bit more about the follow-up appointments that you need to keep up with? What doctors do you see on a regular basis? Lauren Haranhan: So, on a regular basis, I see my ENT, he kind of heads my medical team, I would say. I'm always in his office getting hearing tests. He schedules my MRIs and looks over the scans as well. I also have a neuro oncologist on hand. She also looks over my scans and then also, if I needed an alternative treatment, I guess you could say, which would be Avastin, she would be the one to prescribe that for me and that would only be if my tumors started to grow or I showed other signs or symptoms and those are only for the tumors located within my ears. So, those are the two doctors that I see consistently, a couple of times a year. I also have to see an eye doctor at least once a year to check my eyes, too. Jessica: And we talked a little bit before this about your genetic testing process, can you tell us a little bit about that because I know it's not maybe typically the journey for genetic testing. Lauren Haranhan: So, I had genetic testing done when I went to go see my neuro oncologist and the genetic counselor, and the results came back that I didn't have the NF2 mutation, so that pretty much was just saying it's not in all of my blood cells. It definitely doesn't mean that I don't have it. It's probably just a smaller percentage, a more mild case. So, I then was following up with further genetic testing, which dives a little bit deeper into your cells and your genes and unfortunately, I haven't gotten the results yet from that because COVID happened and all the labs unfortunately were close and on lockdown. Jessica: So, what are some of the tools that have helped you become successful on this journey, which again, just started a year and a half ago? So, you're new to this, but seemed like a professional at this point. So, what are some of the things that have helped you? Lauren Haranhan: I would say one of the biggest tools is conducting my own research that is reliable, not going off of just any Google website that you find, not going off Facebook groups, really finding accurate research that scientists and doctors and specialists have done to learn about the genetic condition and then also my doctors, listening to their advice or suggestions, that's really been the biggest tool. And then also just support from my family and my friends, I think helps you cope with having a rare genetic disease. It makes life a little bit easier on those bad days that you have. Jessica: What are some of the biggest challenges? Lauren Haranhan: One of the biggest challenges for me and again, everybody's different depending on how severe their case is, but one of the challenges for myself would be my hearing. I have single-sided deafness, so it's hard to hear faraway noise, like knowing where noises are coming from. It also is exhausting. My brain is kind of working on overload just only hearing out of one side. Loud noises bother me. I get frequent headaches. Those to me are the challenges that I have daily, I would say, and just kind of not knowing what your future holds. You have your future usually planned out in your head of what you want your life to kind of look like. And then when you're diagnosed with a genetic disorder or disease like this, plans change. You kind of have to let go of certain things that you once thought what happened within your life. Jessica: And can you tell us a bit more about how you have found reliable information? So, if you look online or if you're talking to your doctors, what types of things do you do to determine if something is good information or not so good information? Lauren Haranhan: Well, one of the things is just looking at the source itself, I would say. That to me is one of the biggest things that I focus on, like where is this actually coming from. There's common things that you'll see about NF2, but then sometimes you'll read other things that may be more towards NF1, just because they share the same title in the beginning, they're very different disorders. Another thing that has helped me is I volunteer with a nonprofit, so getting information from them as well. They work hand-in-hand with researchers and labs and scientists, so that is really reliable first-hand information. Jessica: And that's the perfect leeway to our next question, which is can you tell us a bit about the patient advocacy group that you are working with? Lauren Haranhan: So, I work with a nonprofit called NF2 BioSolutions. It is an advocacy group full of parents and patients and just volunteers, family members who want to come together to find a cure. Our goal is to use gene therapy to accomplish this, and my part as a volunteer is helping with fundraising and spreading awareness because that will help us fund different labs that we have doing gene therapy projects for us. We really want to get researchers on board and interested in NF2 so that way, we find a cure for NF2 using gene therapy. Jessica: And what are some ways that family and friends can support someone with NF2? Lauren Haranhan: Honestly, just understanding that the patient is going to have good days and bad days and understanding that some patients look completely fine from the outside, but that doesn't mean that it's still not a struggle. I mean, fatigue is a huge thing, headaches. Just knowing that it affects everybody so differently, and just because it might not be seen, it doesn't mean that that patient or person isn't going through something. Lauren Haranhan: Also, just helping them stay motivated and hopeful is the biggest thing because as I said before, you have your good days and your bad days, as does anybody else, but sometimes it's a little bit harder when you're battling your own body with a genetic disorder. And I would say encourage that family member or patient to get involved. Spread awareness. If you can't do fundraising, definitely spread awareness. Let people know that you have it. Sometimes it's easier to let people know, so you can talk about it and it's not a secret. Let the world know what NF2 is because that's how we're going to make a change. Jessica: What is your advice to those struggling with a diagnosis or maybe to someone who is having one of those bad days? Lauren Haranhan: Stay hopeful, surround yourself with people who bring you joy, get involved. To me, getting involved with NF2 BioSolutions was probably one of the best things I could have done for myself because I feel like I'm a part of something, I feel like I'm making a change and I'm making an impact. I'm not sitting back letting this disorder take over. I'm still in control. And also taking care of yourself, I think that's a big thing, knowing that it's okay. If you need a break, it's okay if you're having a day, but tomorrow, make it a different day. Look for the positive things in life still, because somebody always does have it worse. Just stay hopeful. Jessica: Is there a way that you've connected with other patients that has helped you through those times or do you have advice for people with NF2 and how they can find other people with NF2 to connect with? Lauren Haranhan: So, yes, definitely. I've connected with people who have NF2 through NF2 BioSolutions actually. We have local ambassadors. We're trying to get one in every state, but even if your state doesn't have one, there are states around you that do and we are a group of volunteers working towards one cause and that is to find a cure for NF2. So, talking with them, you really become close. Some of the people I haven't met, but yet I've talked to multiple times. Lauren Haranhan: I was actually able to meet a few of the ambassadors last February when I went to Washington D.C. with them. Everybody kind of joins force. We're all on a mission and you become close that way and they help you when you're having those bad days, too. They encourage you, they've been there, they've done it, they understand, which can be hard because people around you who don't have this, they understand to a point. So, when you can really connect with somebody and text them and like, "Hey, I just got my results. Looks good or it looks bad," like just having that support of somebody who truly understands is the best way. Lauren Haranhan: But people can definitely go on the NF2 BioSolutions website and find a local ambassador near them and we are all more than happy to reach out and start a friendship with somebody to help them. Jessica: That's great. What do you think makes a patient and family facing a diagnosis of NF2 most successful? Lauren Haranhan: I would say, listening to your doctor's advice, making sure that you go to an NF2 specialist. I've found through the year and a half that when you go to your local doctor, they don't really know what an NF2 is. It's not very well-known, so making sure that you go to specialist who know about NF2 that is going to make your just journey, I guess, more successful. You're going to have information that's more current, more up-to-date and safer, I would say than find somebody who's not pretty sure what NF2 is. Jessica: And the nice thing I think about the patient organizations, too, is even if there might not be a specialist in your area, sometimes some of those specialists are willing to talk to local physicians, so that's often good for patients, too. Lauren Haranhan: Yes, and there are many specialists, too, who also will do conference calls with you. When my journey first began, there were specialists out in California that honestly I could say I leaned on them so much, just to get me through that initial shock and hearing them say, "It's going to be okay," helped me form a plan, and I have specialists out in Boston as well and even down here in Florida. It's really relying on those doctors. They want to help you as a patient as much as they possibly can. Jessica: And what are your hopes for the future of NF2? Lauren Haranhan: Well, my hope for the future of NF2 is that we can cure it. That's our goal. We're trying to cure it through gene therapy or trying to find better treatment options or trying to make life more enjoyable for people who are struggling and have really been affected by it. Jessica: Thanks to Lauren. Jessica: Our next conversation is with President and CEO of NF2 BioSolutions, Dr. Nicole Henwood. Dr. Henwood is the parent of a child of NF2 as well. Let's hear from Dr. Henwood. Jessica: All right. Dr. Henwood, would you mind introducing yourself? Dr. Nicole Henwood: Sure. My name is Dr. Nicole Henwood. I am the President and CEO of NF2 BioSolutions. Jessica: And how did you begin your journey with NF2? Dr. Nicole Henwood: My son AJ, who is now about to turn nine later this week, was diagnosed with NF2 when he was six years old, so about two and a half years ago. So, at that point, after some time of grieving his diagnosis, I decided it was time to do something about it and that's how I started down this pathway. Jessica: And can you share some advice for parents and patients in the community that are potentially facing a new diagnosis and what resources were maybe the most helpful to you in the beginning? Dr. Nicole Henwood: Well, that's a tough question because it was really kind of hard at the beginning and I had a little bit of a jumpstart, because I had just very briefly in college worked in a gene therapy lab, so I had a little bit of an idea on how to start, but that's really hard. The first thing really you have to do is see if there's an organization that is already working on the disease that your family or loved one is affected by. Dr. Nicole Henwood: There are 7,000 known and probably more unknown rare diseases and a lot of them already have a foundation or another family who's taken up the cause, so that's really the first place to start. And then if there's obviously some things already in existence, joining forces. The more people fighting for any given disorder, the better chance it has of moving forward but if not, then starting from scratch is okay, too. There's I know a lot of rare disease families who have moved the needle a lot on their disease when they were the first one or maybe one of six in the whole world with a certain diagnosis. Jessica: Can you tell us about an NF2 BioSolutions? Dr. Nicole Henwood: Sure. So, we are a 501(c)(3) Public Charity. We were deemed a charity by the IRS in mid-2019, so it's only been a little over a year with all of this, so we are all volunteer run. So, NF2 stands for neurofibromatosis type 2 and there are three types of diseases that fall on those category, NF1, NF2 and NF3, that was recently renamed to schwannomatosis. So, we are the only organization that focuses just on our subtype of neurofibromatosis. There's a lot of great organizations that deal with NF as a whole, but we wanted something a little more specialized. Dr. Nicole Henwood: So, we started the nonprofit and we're all run by family members or patients themselves or a few just kind of solid volunteers also that just want to help out in the rare disease world. So, we started really small with five board members and then we have grown to 11 board members and 35 ambassadors throughout the world, U.S. and across overseas as well and we're starting a chapter. We actually just completed the process, so it was a very long process in England, the UK chapter and are thinking of starting one in Germany and France as well. Dr. Nicole Henwood: So we're growing rapidly, and I think I really attribute that to the need of there being an organization devoted to the specific subtype of NF2. So, our goal is to find a treatment. We're focusing on novel therapies, so I use the word here loosely, but a treatment that is longer term, fixing the underlying cause, meaning the genetic alteration that leads to NF2. So, we're looking at things like gene replacement and gene editing and things that might free our population or community from these harsh surgeries and chemotherapies and things that are really a lifelong thing right now for all NF2 patients. Jessica: How many different groups are working on projects right now for a treatment or cure for NF2 through NF2 BioSolutions? Dr. Nicole Henwood: We have four, hopefully soon to be five, different organizations or labs that I should say that we're working with. So, two are gene replacement or gene addition, which is the traditional gene therapy approach, one is a cytotoxic approach to actually kill existing tumor cells, and then our fourth project is a tumor bank. So, we just established a biobank where tumor samples will be stored and they're all open access. They get DNA sequenced and hopefully RNA sequenced as well, and that will all be on an open access Cloud as well as the tumors themselves. Any lab that's interested could order sections of tumor to study, so we're hoping to attract new researchers and also give a boost to the labs that are already working on NF2. Jessica: What are the current needs of NF2 BioSolutions moving forward? Dr. Nicole Henwood: I think, unfortunately, the two things that are the needs for most rare diseases are our needs as well, awareness and funding. It being a rare disease most people have never heard of it. There's a lot of patients who have NF2 that never get referred to a tertiary care center. We really need the general community of neurologists and family practice physicians and internists and neurosurgeons as well to understand what an NF2 is and make sure that all of these patients have the knowledge that will allow them to participate in finding a therapy and that includes sending tumors to the tumor bank, so that we can study them. It includes getting involved in our organization, it includes fundraising, it includes volunteer manpower hours, so getting the whole community together through awareness and then of course, awareness leads to funding. So, that's our two basic needs at this point. Jessica: How can families who have a diagnosis of NF2 or patients with a diagnosis of NF2 become involved in things like the tumor bank? Dr. Nicole Henwood: The tumor bank is through Children's Hospital of Philadelphia, but they take adult tumors as well. They make it really easy. If you already had a surgery and have tumor that has been stored and frozen, they take care of all of the paperwork and all the legwork of getting that tumor transferred. And then anything going forward prospective collection of tumor samples with upcoming surgeries, they take care of it as well also. You just have to let us know, send us a message through our website and we can introduce you or go direct. Dr. Nicole Henwood: It's called CBTTC, Children's Brain Tumor Tissue Consortium to them and let them know you're interested in donating a tumor for NF2 research and they are so amazing. They send all the supplies to the surgeon, everything, so that when they take out the tumor, it's just right there, packaged, labeled and off it goes and it's in the tumor bank forever. Jessica: And what are your hopes for the future of NF2? Dr. Nicole Henwood: I am so hopeful that as technology advances, which is getting more advanced even year by year and month to month, things that we weren't able to do a few years ago in terms of genetic mutations are becoming more and more feasible and likely to be applicable to humans and being able to translate basic science research to the clinic. My hope is that we find a way to make this a lifelong managed chronic disease rather than acute and acute life-ending, life-spoiling disease like it is now. Dr. Nicole Henwood: You look back at things like type 1 diabetes. It was a death sentence for young children, and now it's possible to live a very long healthy life with some management. So, that's really what I'm hoping for as best case scenario. Obviously, the ultimate solution, the best thing that could ever happen would be a cure, but we all take that with a grain of salt and just know that some lifelong therapies, even if they could control this and buy us some time would be fantastic because things change every day. Dr. Nicole Henwood: In 10 years from now, we may be able to just practically flip a switch and correct the mutation, but right now, we're still pretty far away from that, so anything that can extend the time, the healthy times that we have and lead us closer to an actual true freeing treatment from these terrible surgeries and chemotherapies and other drugs the patients are on now is a path that we're searching for. Jessica: From your perspective, can you share it bit more about what the next step would be? So, in these different projects that are working on cures and treatments for NF2, how does that become more mainstream in simple terms, maybe for people to understand? Dr. Nicole Henwood: Well, it's once we show that something works in cells, then energy cells are taken from a person or engineered to have the NF2 mutation, which we do have some data that shows that when things are working in cells, then we go to animal models where we try to cure an NF2 mouse and that also, we have a few, actually two of our projects has shown very good data in mice. The next step is to bring it to humans to the clinic, but before we do anything in humans, we have to show that it's safe. So, the very first step is a safety, what we call a toxicology study where they test the therapy, independent lab and look for side effects things like inflammation or immune responses that could be unsafe. Dr. Nicole Henwood: And then once proven safe, then we started human clinical trial, which also the first phase one of a clinical trial is a very small study, 10 to 12 people at low doses, starting very low and working up to show that it's safe in people and then we go to bigger scale study, phase two and phase three, where we look to show that it works, so its efficacy. Once the FDA agrees with us that it's safe and that it works then that drug or therapy becomes approved, an FDA-approved medication or therapy, and then it's open to the general population. Jessica: And at what point does a pharmaceutical company come into play? Dr. Nicole Henwood: That's changing a lot. Pharmaceutical companies can come in really at any stage. Typically, they'd like to see that a product is safe and has some efficacy before they come in, but we've seen other diseases and organizations or pharmaceutical companies as early as the preclinical stage, which is in animal models, but it could be anywhere as latest phase two or phase Three, wherever there's a company that comes along that this medication or therapy fits what they're looking for in their platform in their company, it's just all about finding a partner. So it can happen at any point, but I would say most commonly around the phase one trial or so. Dr. Nicole Henwood: But sometimes I think some companies, big pharmaceutical companies do their own research. So if they're interested in curing a particular disease or finding a therapy, they do in-house research as well. All of our projects are through academic institutions, so we do not have an industry partner at this point. And as far as I know, there's very few biotech and pharmaceutical companies working on NF2 at this point, I think just one. Jessica: So the hope would be, of course, to continue this research and continue getting the word out there for NF2 and we have the same hopes, of course for the future of NF2 as well. So, thank you so much for all of your work on this, but I really want to make sure that people know how they can get involved and volunteer with NF2 BioSolutions. Dr. Nicole Henwood: Well, we're always looking for new ambassadors, so just because there's maybe a state or a country that already has an ambassador, it doesn't mean that we can't use more. All our ambassadors appreciate a buddy system, so they have somebody else to help with planning of events, so definitely contact us about being an ambassador, even just bringing pamphlets if you have an NF2, and you're going to your local care team, be it an NF clinic or not, bringing some pamphlets along and sharing it, spreading the word about what we're doing. Dr. Nicole Henwood: Of course, fundraising, holding an event, an online auction after the pandemic maybe even a run or a gala of some sort, or anything like that would be always more than welcome. And that's how we got started with these grassroots fundraising efforts via a Facebook, birthday fundraiser, or anything really. Any little bit helps, so we don't turn away any help or any volunteers, so definitely, come to us if you want to be involved. We'll find a place for you. Jessica: Thank you, Dr. Henwood. Jessica: We would like to thank our guests once more for their time and commitment to NF2. Jessica: We all find ourselves with a small bit of information that only leaves us wondering, "Okay, what now?" So, what now? We know that hearing from these experts is only the beginning for you. That's why we've taken the information here and added additional resources, explanations, links, and references for you in a downloadable guide on NF2. You can get your free copy of that guide by going to raredisease.com/NF2. There, you can download a recap of this episode that lists the key points as well as several links and resources for you to further explore. Jessica: Finally, if you need to speak with someone directly about NF2 or your personal situation, we're here to help. Visit raredisease.com/help to get in touch. Jessica: We are standing by. This is Rare Disease Connection, a production of aspecthealthandraredisease.com.