Neurofibromatosis Advocacy and Community Building with the Gilbert Family Foundation

Episode Transcript

Dr. Correa:
From the American Academy of Neurology, I'm Dr. Daniel Correa.

Dr. Peters:
And I am Dr. Katie Peters, and this is the Brain and Life Podcast.

Dr. Correa:
Welcome back to the Brand and Life Podcast. Katie, how are you doing today?

Dr. Peters:
I'm doing great. It's been a good weekend working on some papers and getting back to work after I guess a little bit of a holiday.

Dr. Correa:
It's been a very exciting week for me here in the Bronx and at Albert Einstein. You probably heard that a donor gave a huge donation to make medical school free. I was with our team at Einstein meeting with a group of doctors and researchers, educators, and community members, that are trying to improve health and opportunities in the Bronx called Bronx Hope. Really, it made me step back and think, really who are the leaders in our community for brain health? I think it's really the patients and the advocacy organizations.

Dr. Peters:
I agree, and in thinking about who really leads advances in neurologic conditions and neurological illness, it is not only the physicians, the providers, the researchers, but it's also who's impacted by the illness itself, who does it touch? It can often touch our patients, our caregivers, and they can in turn develop into their own organizations, own advocacy groups.
One of my great partners I get to work with is Brock Green at Oligo Nation. He has two sons with brain tumors, but he calls himself a care guider and developed an advocacy group around it.

Dr. Correa:
Yeah, I think we have seen countless examples within the community living with neurologic conditions of this. We did an episode interviewing advocacy members within the community for multiple sclerosis. We've seen within the communities for ALS and epilepsy, that organizations move things forward, not just research, not just access and development of new treatments, but even just expanding the resources that are available to the community. Just social work services and educating people about living with a condition. We see this in even local, really focused local communities within the Epilepsy Foundation, where they work around the country to help individuals in each area.

Dr. Peters:
I think what's important about these types of advocacy groups is that it does include patients and caregivers, and who is best to really know what they need to impact themselves for their quality of life, their day-to-day living? So this is why it is critical that we reach out to them as physicians so that we can learn from their experience and what's important to them.

Dr. Correa:
So I hear that you're expanding our awareness about another group and in another condition that is helping to advocate for our community.

Dr. Peters:
Yes, I got to speak with the Executive Director of the Gilbert Family Foundation. They seek to advance research into a condition called neurofibromatosis. The Executive Director is named all Laura Grannemann, and we had a lovely conversation about her role, her background, and what the Gilbert Family Foundation does. The Gilbert Family Foundation was actually founded by Dan and Jennifer Gilbert because their son had passed away from neurofibromatosis.

Dr. Correa:
Now, I could imagine several listeners being like, neurofibromatosis, blah, blah, blah, what? So what's neurofibromatosis for our listeners?

Dr. Peters:
So it is a genetic condition associated with brain tumors and skin tumors and other conditions. I'm going to just hope that our listeners will learn a great deal from medical expert, Dr. Jaishri Blakeley, who is a neurologist and Director of the John Hopkins Comprehensive Neurofibromatosis Center, and Director of the Neurofibromatosis Therapeutic Acceleration Program.

Dr. Correa:
So this is a condition that can affect the nerves in so many different parts of our body and really impacts individuals significantly. So, I hope all of you get a chance to stay and listen to our medical experts so you really get to learn more about the condition itself, along with the advocacy work that the Gilbert Family Foundation is doing.

Dr. Peters:
Hello, Brain and Life podcast listeners. It's again, your co-host, Dr. Katie Peters for the Brain and Life podcast.
In a patient's journey with a neurologic disorder or illness, getting support from advocacy groups, it's vital, it's truly needed, and this is true for the Gilbert Family Foundation. It's an advocacy group that focuses on advancing groundbreaking, cutting edge research to treat a condition called neurofibromatosis. This is a genetic condition that is associated with tumors of the nervous system.
Today we are going to be joined by the Executive Director of the Gilbert Family Foundation, and it's Laura Grannemann. So Laura has two hats. She's the Vice President of the Rocket Community Fund in Detroit, Michigan, and the Executive Director for the Gilbert Family Foundation. She has a degree in international development from Georgetown University and now brings her talents to lead projects to advance research and advocacy for patients with neurofibromatosis. Laura, welcome to the Brain and Life Podcast.

Laura Grannemann:
Hi, thank you so much for having me, Dr. Peters.

Dr. Peters:
Yes, thank you so much for being here. Tell me more about yourself and your career.

Laura Grannemann:
Yeah, I have a background actually in international development. I spent a lot of time in China, in Burma, in Thailand. Then I came back to the city of Detroit really wanting to take some of those talents and invest it here in my home state, I'm from East Lansing. I got connected with Dan Gilbert about 10 years ago, so I started working with Dan and Jennifer 10 years ago. At the time, the Gilberts were extremely passionate about the city of Detroit and wanting to make a big impact here. They were doing that in really thoughtful ways personally, but we didn't really have a lot of strategic philanthropy at Rocket Companies, which is what Dan and Jennifer are founders of Rocket Companies, which is the nation's largest mortgage lender. So I had the opportunity to work directly with them to build up a lot of investments in the city of Detroit. We focus a lot on housing stability, arts and culture, public space, here in the city.
Then a couple of years ago, about three years ago, we made a $500 million commitment to building opportunity and equity in the city of Detroit. That's a joint commitment between the Rocket Community Fund and the Gilbert Family Foundation. So, a lot of listeners are probably saying, why is she leading both organizations? That is why. We made this joint commitment and we really wanted to be thoughtful, strategic, and coordinated across the two entities, so I have the privilege of leading both organizations. That really meant also, taking on a lot of the neurofibromatosis work. So I'm not a scientist, but I am a great enthusiastic advocate for this work. It's been really interesting actually, to see how there are a lot of intersections between neurofibromatosis research and how we invest in and approach issues of community and economic development in the city of Detroit as well.

Dr. Peters:
I completely agree, and thank you for wearing these two different hats and bringing your expertise to this because it is so needed. I agree with patients, I'm a neuro-oncologist in full disclosure, and it really does take a village, it takes an advocacy, it takes action groups, to really come behind a disease such as neurofibromatosis.
Now, can you share with the listeners a little bit of the history of around the Gilbert Family Foundation, particularly in regards to NF?

Laura Grannemann:
Yeah, absolutely. So the Gilbert Family Foundation was officially founded in 2015, and the original goal was really to advance cutting edge research to try to end, to eradicate neurofibromatosis. Unfortunately, Dan and Jennifer's son is affected by neurofibromatosis, Nick Gilbert. Truly, unfortunately, we lost Nick to his neurofibromatosis earlier this year, back in May.

Dr. Peters:
I'm so sorry.

Laura Grannemann:
Yeah, it's been a really, really tough year but one thing that I can say that's definitely a point of pride is that Nick had an incredible spirit. He never let his neurofibromatosis diagnosis define his life. He did everything he wanted to do. He climbed mountains, he traveled, he ate a ton of macaroni and cheese, and most importantly, he had an incredible group of friends and family who absolutely loved and supported him. So it's been really heartwarming to see all of those people continue to come together. We have an annual gala, and we had that gala last November, and it was a hugely emotional night. So many people coming together and broke so many records in terms of fundraising. So I know that we're going to do his legacy proud and his friends and family are going to continue to keep his spirit alive.

Dr. Peters:
I think it's so important to have organizations like the Gilbert Family Foundation really rooted in looking into these rare neurologic conditions and rare cancers. I feel like a lot of times that these are diseases that don't get as much, I guess, air time or funding just because they are less common, but they can have really huge impacts because as a neuro-oncologist, the gene that's involved with neurofibromatosis is really the stepping stone of so many other cancers and so many other developmental neurologic conditions that you have an opportunity to be at that touchpoint just by understanding that disease.
I want to make sure that our listeners know that even though I call it a genetic disease, it's because it's due to a gene mutation, it's not necessarily inherited down family lines. It can just pop up sporadically, just like somebody can have different color hair or different color eyes. It's not something necessarily that you inherited in that family line. So I just wanted for patients, to give clarification to our listeners.
Now for the Gilbert Family Foundation, how do you engage with the NF community? Do you have panels of patients? Do you have panels of caregivers that you work with?

Laura Grannemann:
So we have several different initiatives at the Gilbert Family Foundation. We focus on a few of the most common manifestations of neurofibromatosis, and that means that we're really looking at the intersection of neurofibromatosis and brain tumors, the intersection of neurofibromatosis and vision loss, so we're really focused on vision restoration. Then last is a connection with gene therapies. We have a gene therapy initiative. Speaking to your point earlier, it really is because of that genetic modification, that is the underlying cause for all of the different manifestations that we experience within the NF community. One of the most difficult things about treating neurofibromatosis is that there are so many different ways that the disease can manifest. Each person's patient experience can be slightly different. So when we look at gene therapy, that's really, really important because that is the trigger that causes each one of those individual manifestations.
The last thing that I want to mention, it's not quite an initiative, where each initiative has a group of researchers that come together on a regular basis. They're essentially our panel, they're peer reviewing everything that we're looking at and considering funding, and we're working really with them on a regular basis to think about our strategy and refine our strategy going forward. But the last thing I want to mention is that earlier in 2023, we had the opportunity to launch a partnership with the Henry Ford Health System and Michigan State University to start an organization called the Nick Gilbert Neurofibromatosis Research Institute. This will be a physical brick and mortar institute in the city of Detroit, so exciting, where we will be really bringing all of this research together. The basis of that, this new research, is going to be in organoid technology.
So organoids, for anyone who's not familiar, is essentially like a little mini organ that's built in a dish. What you can do is take patient genetic material, you can take genetic material from healthy tissue of a patient and you can take tumor material from a patient and you can grow a mini, let's say brain, and then you can rapidly test treatment options on the healthy tissue and the not healthy tissue. That allows us to hopefully be able to go much faster in identifying what treatments are attacking the unhealthy tissue while not harming the healthy tissue. So we're really, really excited about that opportunity, big announcement this year. We hope that that can be a culmination point for all of this research going forward.

Dr. Peters:
Laura, can you clarify, has that broken ground yet or you're waiting to break ground?

Laura Grannemann:
We're waiting to break ground. We just announced it back in September, and it should be fully built by 2027, but we are already starting the foundational technology and research associated with this. We aren't waiting until we have the full brick and mortar up and running. We're making some investments along the way in organoid technology so that we will be fully ready to go when we've got that brick and mortar space.

Dr. Peters:
That is really exciting. That group at Henry Ford, the neuro-oncology group is great, and I love the way you're partnering with them. That's what organizations like the Gilbert Family Foundation are really seeking to do. Now, do you have any advocacy projects? You mentioned the gala, is there any other advocacy work within the Gilbert Family Foundation?

Laura Grannemann:
Yeah, so the beNeFit, it's a little bit of a play on words because it's the word benefit, but capital N, capital F, is our main fundraising event every year. We work with both the Children's Tumor Foundation and with a 501(c)(3) called NF Forward, to fundraise for primarily research. So continuing to contribute to this cutting-edge research that we've been talking about. But of course, CTF also does a ton of patient advocacy. They have been really fantastic partners with us, that's the Children's Tumor Foundation. They are just a wonderful group that does everything from investing in research to also supporting patients who are going through this journey. We've really been emphasizing storytelling on all of our platforms. So of course the benefit is the culmination of this, but we have as well a big social presence, lots of video storytelling. We're lucky to have a lot of great assets and partners in building some of those videos and opportunities to honor different NF advocates and patients.

Dr. Peters:
That sounds wonderful. Now, do you engage with pharmaceutical companies to try to keep them in to the space of staying in research for patients with NF?

Laura Grannemann:
Yeah, we do, absolutely, it's a great point. There is a funnel, if you will, in terms of how much you have to put in at the beginning into research in order to get to an actual treatment at the end. Unfortunately, it's thousands of different treatments you have to test and try before you get to the one treatment that works. I believe the average is about $1 billion that you have to invest in research before you get to that treatment. That's again, for anyone who's newer to the idea, this was something that was incredibly difficult for me to get my mind around. That is really why it's so difficult for pharmaceutical companies to ultimately see that pathway to profitability, because they have to overcome that huge research investment gap. So it's very, very important that we're bringing those companies alongside with us. Luckily we have been able to support some research that has led to a few drugs. Selumetinib is a great example that has now gone through the research process and then FDA approval and now it is available to patients.

Dr. Peters:
Yeah, that was a huge development. It was published in the New England Journal of Medicine and on one of the rare... some of the tumors associated with NF called a plexiform neurofibroma, which is not necessarily what we think of in the brain, but can cause a lot of disfigurement and pain for patients. So I think that again, it highlights the very varying phenotypes that we can see with NF.
I think one of the other things that's unique about NF, it does start in childhood. So it's wonderful that you're partnering with the pediatric brain tumor advocacy groups, but it can affect adults throughout the continuum. Is the Gilbert Family Foundation, do they think of it as across all ages type of disease to study?

Laura Grannemann:
Neurofibromatosis is one of those that crosses all demographics, it affects everybody equally. So we see regardless of ethnicity, regardless of race, regardless of gender, there's a crosscutting effect of neurofibromatosis. You know what? It's actually great for us to think about it as not just a children's tumor disease, but as something that affects all ages because that means that we're having success in making sure that people are finding ways to live their lives successfully despite a neurofibromatosis diagnosis. There's all sorts of different manifestations, so people can live a healthy, long life with neurofibromatosis, but it also means that ideally we are finding treatments that allow people to remain healthy throughout a long and happy life.

Dr. Peters:
Yeah, treatments that will be easy on them, easy on their caregivers, have less morbidity associated with them. I'm just going to quiz you a little bit on your international development background, and as it pertains to this, because you just mentioned this is a disease that's across all ages, all ethnicities, all different types of people. Do you ever see you using your international development, I guess background, to go global with the Gilbert Family Foundation?

Laura Grannemann:
That's a great question. We do feature and honor a different individual every year, and I believe we've featured and honored three or four, maybe four different people from different countries.

Dr. Peters:
That's wonderful.

Laura Grannemann:
[inaudible 00:21:29] England, we had someone from China, someone from Africa. Anyway, there's been a few. So it's absolutely not simply in the United States. We have absolutely funded investments research all around the world, so this has to be everybody locking arms. It can't just be defined by our own borders.

Dr. Peters:
I like that. So you can be the spearhead of that because of your background. So I think that's wonderful, Laura. Well, Laura, thank you so much for sharing your important work with the Gilbert Family Foundation. Do you have any last pieces of information for our Brain and Life podcast listeners?

Laura Grannemann:
Yeah, I would just leave everyone with the idea that if you didn't know about neurofibromatosis, I would challenge you to learn a little bit more and share it with your networks because the more people know about this, the more we are going to be able to build a great advocacy ecosystem and support network for patients who are experiencing neurofibromatosis diagnoses. So visit NFForwardDetroit.org is a great place to just get access to more information and learn a little bit more. Hey, come on out to Detroit for one of our future benefits, and you can meet the team, you can stay engaged that way, and I promise you'll have a great, fun night.

Dr. Peters:
So Laura, thank you so much and thank you so much to the Gilbert Family Foundation. I think that this is so important to have this advocacy work for this critically important disease.

Laura Grannemann:
Thank you so much. I appreciate it.

Dr. Peters:
As always, thank you to our listeners and I'm wishing all brain wellness.

Dr. Correa:
Can't get enough of the Brain and Life podcast? Keep the conversation going on social media when you follow @NeuroDrCorrea and @BrainandLifeMag, or visit Brainandlife.org.

Dr. Peters:
Hello Brain and Life podcast audience, thank you for joining us today. I'm your podcast co-host, Dr. Katie Peters, and I'm honored to introduce our medical expert, Dr. Jaishri Blakeley, who will be discussing the management of neurofibromatosis type one, through her experience as a neurologist and neuro-oncologist. Dr. Blakeley is the Marjorie Bloomberg Tiven professor of Neurofibromatosis in Neurology, Oncology and Neurosurgery at Johns Hopkins School of Medicine. She's also the Director of the Johns Hopkins Comprehensive Neurofibromatosis Center and Director of the Neurofibromatosis Therapeutic Acceleration program. Through this program, Dr. Blakeley has supported and collaborated with many researchers across the globe that are enabling meaningful therapeutic development of neurofibromatosis type one and type two associated neoplasms. Her research and programmatic efforts are all in surface of improving outcomes for patients and their loved ones that are dealing with NF1, NF2, schwannomatosis, and primary brain tumors. We are very excited to welcome Dr. Blakeley to the Brain and Life podcast. Dr. Blakeley.

Dr. Blakeley:
Hello, it's so wonderful to be here. Thank you for having me and thank you for asking about neurofibromatosis.

Dr. Peters:
Wonderful. I know I introduced you, but could you just tell us where you're joining us from and what you do, day to day?

Dr. Blakeley:
Yeah, absolutely. I am joining you from my office here on the Johns Hopkins Hospital campus in Baltimore, Maryland. I do a couple things day to day. I take care of people who are living with neurofibromatosis type one or NF1, neurofibromatosis type two, schwannomatosis, because we've recently combined those terms, and the other schwannomatoses including LZTR1 and SMARCB1 schwannomatosis. I do that through a dedicated clinical program for people with NF1 and the schwannomatoses. I also run research through NTAP, the program that you mentioned. NTAP is wholly focused on finding cures really, for cutaneous and plexiform neurofibromas that people with NF1 live with. Then after I do all of that, I have the pleasure of working with residents and fellows to teach them neuro-oncology, and I do that in our brain cancer program.

Dr. Peters:
That's wonderful. I will say, I'm going to give a plug. Dr. Blakeley was my chief resident when I was also at Hopkins.

Dr. Blakeley:
Just a couple years ago.

Dr. Peters:
Just a couple years ago. So for our listeners, Dr. Blakeley, can you just tell us, what are the basics of neurofibromatosis?

Dr. Blakeley:
Yeah, so as I mentioned, there are categories that all fall under the big umbrella, the neurofibromatoses. The first and most common is neurofibromatosis type one. Neurofibromatosis type one affects one in 2,600 people around the globe, all ethnicities, all backgrounds, everyone is equally affected, one in 2,600. The neurofibromatosis type one is caused by a alteration in the NF1 gene that lives on chromosome 17. While it is 100% penetrant, meaning if you inherit the gene, you have the condition, it's widely variable in how it presents. So some people can have NF1, we would make the diagnosis, it is diagnosable. They're not "carriers," they have the condition, but they have really, really mild manifestations and they barely know, might not know. We often diagnose adults when their kids are diagnosed. Then there are other people who know early in their life because they have pretty significant manifestations. The manifestations of NF1 can involve all parts of the nervous system, brain, eye, spinal cord, peripheral nerve, other parts of the body like bone and blood vessels. So when you have an NF center, we are trained to pay attention to all of those issues on behalf of our patients. We're the health gatekeeper.

Dr. Peters:
I like that term, the health gatekeeper. I think that's... because it's not just about helping diagnosis a condition, it's really, what are the next steps?

Dr. Blakeley:
Yep, and really, thank goodness, many of the times when someone comes to see us in clinic, I get to visit with them and hear about how their life is and they're doing great and they don't have any health needs other than their healthy surveillance. But my job is to prove that so that they can go on for another year and feel great.

Dr. Peters:
What is NF2?

Dr. Blakeley:
So NF2 is a wholly different condition, and actually the terminology just changed through a global effort to try to harmonize what we see in people who are living with the condition, NF2. What we see in the people who are living with NF2 is a type of a benign tumor called a schwannoma. It turns out that schwannomas are common in a couple of heritable tumor predisposition conditions, NF2, and then the schwannomatosis of which we have two genetic causes. One is caused by SMARCB1 and one is caused by LZTR1.
So this new movement is that all of the tumor predisposition conditions that are predominated by schwannomas are one condition, and we call those the schwannomatosis. Then in the schwannomatosis there's NF2 which is the most common, and that is manifest by multiple, the schwannomas. So NF2 is just entirely different in all ways than NF1. The only thing that they share is that it is again, a heritable condition. If you get the gene, you have the condition, and the manifestations can vary across individuals who have the condition. Otherwise, they get different tumor types present at different ages, have different manifestations and have a different genetic background.

Dr. Peters:
You mentioned that it's inherited in some families, but not everybody has a parent or siblings with the condition or even knows another relative that was maybe in their lineage. Can you explain why sometimes it is inherited and sometimes it's not?

Dr. Blakeley:
Absolutely. For both NF1 and for all of the schwannomatoses, NF2 and the LZTR1 and SMRCB1, they are autosomal dominant. So what that means is if your mom or dad has the gene, then there's a fifty-fifty shot that you are going to have the gene, and that's every single time.
So every single time a mom with NF1 has a pregnancy that the result of that pregnancy, that child has a fifty-fifty shot of having NF1. Sometimes they won't, they got the autosomal dominant gene from the dad and not the mom, and 50% of the time they will. That's true of all of the neurofibromatoses. Separately, 50% of all people who are diagnosed with NF1 or NF2 are the first person in their family to have it. That is just genetic vulnerability. These two particular spots and these two particular genes, chromosome 17 for NF1, chromosome 22 for NF2, and some of the other schwannomatoses, are just vulnerable. The analogy I use in clinic, my patients will tell you I'm really into analogies, some are stronger than others, I can admit that. But the analogy I use is that when a baby is being created, there is a fertilized egg and then there needs to be 1,000,000,001 copies made. If at the time of fertilization there is a copy error, then that copy error goes through all 100,000,000,001 copies of the page and you now have that alteration. Maybe that's NF1, when neither of the contributing egg or sperm had that alteration. So that's called a spontaneous alteration and that's 50% of all people who have a neurofibromatosis diagnosis.

Dr. Peters:
Thank you for explaining that, I like the analogy. Now, something else that I think is unique that you've mentioned is you said that if you have the gene, you have the disease, but people can have a milder version of NF1 or a more severe version of NF1. Do we know why there's that variation and what controls that?

Dr. Blakeley:
Oh, I so wish I knew, that's the billion dollar question, I guess I should say in 2024. We do not know why. One of the things that is desperately needed in all of neuro-genetics is more data to support genotype-phenotype studies. What genotype-phenotype means is that there's a particular genetic alteration and then we link that type of genetic alteration to a particular expression in the person, that's the phenotype. A real challenge for NF1 is that there are more than 2,000 different ways the NF1 gene can be altered that results in a condition that clinically is NF1. So we'd have to go find all the ways you can alter the gene that causes this condition and see if we can line it up. That is obviously incredibly challenging, but it's one of the things of why I do research. So we can try to line up these databases that have this. Another analogy, I talk about our genetic testing as each individual's barcode, and if we could get more bar codes in each specific identical barcode, then we could start to find some phenotype data.
But today, we do not know why even identical twins who literally share all of the same genetic information and grew up in the same household. So they both have NF1, they have the exact same barcode of NF1, and one of them will have some sort of manifestations and the other one will have a different sort of manifestations. That's a very active area of research.

Dr. Peters:
That is fascinating. I'll just say, check, more barcodes needed, we need that genetic information. It's going to be studies like those twin studies that I think will really help us understand the disease even better. I appreciate everything you're doing for us to understand it. Now, what are some of the first symptoms if a patient has NF1? What are they presenting with and when do they present with it?

Dr. Blakeley:
Yes. So the most common presenting symptom is skin findings, actually. So often people will present to their pediatrician, you're born with this, every single person who has NF1 was born with it. So depending on how prominent the skin findings are, they will present to their pediatrician and the pediatrician will say, oh, aha, those are cafe-au-lait macules, and you have more cafe-au-lait macules than you're supposed to have. Cafe-au-lait macules are exactly as they're described, meaning they look like coffee plus milk added splotches on the skin. They're totally harmless, they're simply a clinical sign. They can't hurt you, they're not associated with severity of manifestation. There are a lot of conditions that have cafe-au-lait spots, including complete health. I have three cafe-au-lait spots and I've been tested, I have no conditions. So that's the first signal. Then people will look for other things like bone alterations. So a bone isn't formed fully, maybe scoliosis, which is a common way bone isn't formed fully. Then they'll look for something called lisch nodules, which are basically pigmentary changes on the iris instead of the skin. Then we look for neurologic manifestations.
Sometimes the skin manifestations are not prominent or they aren't seen, and people will present with a neurologic manifestation first. In early, early life, like in pediatric neurology, that's sudden vision loss. That can be from an optic pathway glioma, optic pathway gliomas impact about 30% of children with NF1. That's very early in life, and then fortunately and remarkably for any neuro-oncologist out there, optic pathway gliomas are honest to goodness gliomas that spontaneously regress most of the time, which we do not see any other life situation. So if we could understand why those spontaneously regress, we might learn something for all of our other patients with gliomas.

Dr. Peters:
So you really have to tailor your treatment from patient to patient.

Dr. Blakeley:
Absolutely. I call this quaternary primary care. I mean, we try to provide a medical home where we know the person as well as their primary care doctor does, but we just look at it through a lens of expertise about neurofibromatosis.

Dr. Peters:
I love the term, a medical home. I think that really will benefit our patients and their caregivers because they do need a place to land and to feel comfortable with, especially since there's so much variability. I just want to remind our Brain and Life listeners that we did have a recent article in our Brain and Life Magazine about how skin findings can be the first sign of a neurologic condition such as NF1, and also another genetic condition called tuberous sclerosis. So I always tell my providers out there, don't just look at the MRI scan, look at the patient and look at their skin. You need to definitely look at that.
Now, you mentioned some treatment recommendations. What are, I guess, the common treatments? You mentioned that you don't treat these cafe-au-lait spots, but I predict you're going to have to treat the tumor of the optic nerves or the optic chiasm. What is commonly used for those patients?

Dr. Blakeley:
Yeah, so as you just said totally appropriately, it really depends on the manifestation and how it is threatening the person. So for example, the optic pathway gliomas can present and we do the vision exam and we evaluate the patient and they are perfect, and if we just let them grow up, the tumor will go away by itself. So they don't need treatment, but we have to know how to watch for that, what time interval to watch for that, and when to pull the lever for treatment. For optic pathway glioma, the lever for treatment is losing one to two lines on the vision test or having a change in pituitary function that can't be reversed with medical treatment. We have very good treatment for that, it's conventional chemotherapy. The traditional conventional chemotherapy is carboplatin with or without vincristine depending on what side of the Atlantic you practice. There are different practices in the EU and the US, but they're both very effective. However, unfortunately there are some of those optic pathway gliomas that require treatment because of vision loss that then progress despite that treatment.
We've had a recent total change in our practice in NF1 because of the FDA approval of Selumetinib in 2020. That was approved for plexiform neurofibromas, which I'll get to in one second, but it turns out that that drug, Selumetinib belongs to a class of drug called MEK inhibitors. MEK inhibitors also work incredibly well against optic pathway gliomas. So there is right now completing a phase three clinical trial that is comparing Carboplatin Vincristine versus Selumetinib to determine which should be first line treatment for optic pathway gliomas. That's just hugely exciting because there are lots of reasons to not be excited to be using Carboplatin Vincristine in a young child and if there's... But it also works. So we're moving away from, does this work to fix the problem, to does this work to fix the problem and cause the least amount of harm possible? It's always nice to be in that position.

Dr. Peters:
Yeah, and it keeps their quality of life to keep them thriving, because these are usually young children that are affected and they're going to hopefully have a lovely productive life and move forward and that's what you're doing. I couldn't be, I agree with you, that's going to be so exciting to see those face through results.
Now, you mentioned a lot about the vision. You mentioned skin. I assume that you're a neurologist and you're a neuro-oncologist. This is your subspecialty is neurofibromatosis, but it must take really a village, a big team, a multidisciplinary team. Can you describe that for our listeners?

Dr. Blakeley:
Yes, absolutely. So, right, our Comprehensive Neurofibromatosis clinic is centered in neurology, neurosurgery. However, on our regular daily team, we have neuroradiology, genetics, dermatology, plastic surgery, ophthalmology, orthopedics, pathology, whole lot of complex reasons for that. So just in the routine care of our patients, again, I'm the medical gatekeeper, myself and my colleagues in the central NF clinic. Then we will say, okay, now we think we need orthopedics because this scoliosis is progressing a little too fast, or now I think we need ophthalmology because I really need a detailed exam on a pediatric patient for a vision change, which is tricky in a pediatric patient because you don't have the same vision when you're three as you do when you're four is when you're five is when you're six. You need someone who can really delve into that, which I can't do, I'm an adult neuro-oncologist.
So we've had the real privilege and honor of collaborating very closely with all of these sub specialists. I will say, our patient community is so absolutely amazing that the sub specialists always are thrilled to, when I ask for an overbook or this, someone's traveling from Georgia today, can you get them in? It's rare that I get a no, and if I get a no, it's like I can't, I'm traveling and I can't do that. But we have a beautiful partnership with our patient community.

Dr. Peters:
I Agree. A shout out to those patients and also their caregivers. Do you want to comment on any sort of tips you could share with our caregivers of patients with NF?

Dr. Blakeley:
Wow. I mean, yes, they need their own village, first of all. Again, it's so varied. Some people who have NF1 or NF2 schwannomatosis or the other schwannomatoses, really need and benefit from very intense caregiving at home, in their schools, in their work. Some people are 100% independent and we have to again, recognize that person where they are at that point in their life.
One of the super cool and yet challenging things about running an NF center is we take care of people from when they're diagnosed as children to when they hopefully die at 110 happy and well. So other things happen in that time. You get heart disease that has nothing to do with NF, but we have to help manage that in the same space. You go through a pregnancy. How do you think about that in the setting of NF? All of those things.
So similarly, the voyage for the caregiver is as tailored and you have to navigate those really tricky things of, now you have a 16-year-old who has a medical need and they don't want their parents involved, but they're a minor. How do you help everybody on the team work together? The parents, the siblings, the person who's going through the treatment, which is a very different situation than helping a 35-year-old who needs support or a 75-year-old who needs support. So the privilege and the challenge is navigating the path with the caregiver for each person where they are at that point in their life.

Dr. Peters:
Well, I appreciate and applaud your flexibility and your breadth of knowledge and the ability to care for the patient across their continuum and the caregiver across that continuum. So, kudos to you and I think that's just wonderful.

Dr. Blakeley:
And my team, as you say.

Dr. Peters:
And your team.

Dr. Blakeley:
[inaudible 00:43:39] team and we all have different strengths and weaknesses. Like our nurse navigator is the most patient, loving, wonderful person on earth. So she carries all the positive vibes for all of us.

Dr. Peters:
Shout out to those teams. Our teams extend not only to who we work with day to day, but also foundations and advocacy groups like the Gilbert Family Foundation. I had the chance to interview their Executive Director, Laura Grannemann. I believe you've worked with the Gilbert Family Foundation. Can you explain why those types of advocacy groups and foundations are so important for you and your patients?

Dr. Blakeley:
Absolutely. So I have worked directly with the Gilbert Family Foundation, my intersection with them is in two roles. One is that they have a very focused initiative on gliomas in people with NF1, and that is of course a major interest of mine to, I'd like to end gliomas as we know them, period actually, but we'll start within NF1. Also because I run a research organization called NTAP. So we, one of the beautiful things about this space that we all work in, the Gilbert Family Foundation, myself, the Children's Tumor Foundation, which is really the preeminent patient advocacy foundation for all of the Neurofibromatoses, Gilbert Family Foundation is an amazing scientifically-driven foundation focused on NF1. NTAP I hope, is an amazing scientifically-focused foundation focused on NF1. CTF focuses on all of the neurofibromatoses and things like making sure it's clear that we are making good use of federal funds that come through the NIH or the Department of Defense for NF associated research and talking about how important NF associated research is to the general population who copes with similar things.
For example, I mentioned people with NF1, as well as the schwannomatoses present with peripheral nerve injury. So that's a very common event in the general world. Understanding that, having the opportunity to understand and treat that more successfully in a narrow population gives us some windows of opportunity to bring that to the broader population that might have the same problems but from different causes, like diabetic neuropathy or chemotherapy-induced neuropathy.
So these foundations do a couple of things. One of the things they do, as I just mentioned, is CTF, the Children's Tumor Foundation does an amazing job advocating with our legislators at the state level, at the federal level, internationally, about how important it is to keep funding for neurologic diseases active so we can come up with better cures. They also bring the whole community together to share ideas, both the patient and caregiver community and the physician community, and I guess I should say professional caregiver community. They do that through conferences. For example, in April, they'll have their patient and caregiver and physician conference where all three communities come together and talk about what could we be doing better to help people living with neurofibromatosis. Then the other thing like the Gilbert Family Foundation and NTAP do is we drive, we hope, the research that will lead to changes in practice. We partner very closely with our federal agencies to make sure that we're complementing those efforts, not subtracting from those efforts.

Dr. Peters:
Well, Dr. Blakeley, this has been wonderful and we are so lucky to have your expertise and also your desire to work collaboratively to push advances forward for both NF1, NF2 schwannomatosis, thank you so much for sharing your insights and expertise.

Dr. Blakeley:
Thank you so much, it was wonderful to see you again and wonderful to participate in this, an amazing initiative. Thank you.

Dr. Peters:
Thank you, and thank you to our Brain and Life podcast listeners. I wish all of you brain wellness.

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Neurofibromatosis Advocacy and Community Building with the Gilbert Family Foundation

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