Venkata: Hello listeners, welcome to LetsTalkAboutNF, the podcast that facilitates discussion around the topics that affect the NF community. Through this series, we hope to convene patients, caregivers, and clinicians to dive into the social and clinical aspects of NF - whether that’s walking through how multiple individuals deal with a similar issue or breaking down recent clinical trials into accessible and engaging discussions.

I am your host, Venkata Jonnakuti, and today we meet with Mr. Josh Meier, an infrastructure architecture engineer at Salesforce with a wife and daughter, both diagnosed with neurofibromatosis type 1. Now, let’s talk about NF1. Venkata: Hi Mr. Meyer, it's so good to have you on our podcast. Would you mind introducing yourself to our podcast audience?  

Meier: Absolutely. Uh, so my name is Josh Meyer. I'm a software engineer, been in the industry for about 20 years. And at the same time, I've been married to my wife now for going on 16 years, and we have a nine year old daughter, both of them suffer from neurofibromatosis type one, and my daughter is actually almost a year into treatment for a couple of gliomas in her brain using the Selumetinib which was only recently FDA approved last year. So it's been really exciting to see that there was a drug that's been FDA approved and to be able to help and participate in children tumor’s foundations drive to find cures for this disease.  

Venkata: That's awesome, thank you so much for being on our podcast. So your wife and daughter both have NF one, is that correct?  

Meier: That is correct, yes.  

Venkata: Did the manifestations of NF1 presents similarly between both your wife and your daughter?  

Meier: So, for those that don't know, NF actually progresses as an individual ages. So, for example, when I first met my wife she had very few of the physical manifestations that come with neurofibromatosis. So she had, you know, speckles in the eyes and she had the cafe au lait spots, but she didn't have any, or very many, of the visible neurofibromas which are manifested as the bumps on the skin.

As, as an individual, ages, those bumps become more pronounced, there's more of them. As your hormones in your body change, like when she was pregnant with our daughter. She got her, her skin, got way worse. And then as soon as she gave birth it went back to what it was before the pregnancy, which I found fascinating. So, as she's aged obviously it's progressed more. There's constant pain. There's the nerves. They grow on- or the fibromas they grow on the nerves directly. And those happen more and more frequently and you kind of have a chronic pain, type of thing. With my daughter, who's only nine, there really isn't a huge amount of physical manifestation right now, right. She's got the freckled eyes and she's got a couple of cafe au lait spots but nothing major, no visible fibromas. She hasn't had to have anything removed from any sort of nerves. She hasn't had any under the skin either. But we fully expect that those will start to manifest themselves as she ages.  

Venkata: I see. You seem to be unique situation, where able to witness the challenges of living with NF1 , as both an adult in the form of your wife and as a child in the form of your daughter. How are the challenges the same, and how are the challenges, different?  

Meier: So, I did want to. One thing to point out is that it's not actually super unique as a mother or a father for that matter, that has NF, there's a 50-50 chance that it gets passed down to the child. Literally it's flip a coin you, your child may or may not have it. So, it's actually relatively common but are the challenges the same? No. So for my wife in particular, the biggest challenge has actually been to get her to go and take care of things, right? Like there's chronic pain. She's had a tumor glioma or not a glioma- a fibroma underneath her fingernail and she's had it removed a couple of times, and it always grows back and she refuses to do it at this point. So her fingernails are at the point though where, if she brushes it against a bedsheet wrong.

It's, it's just a horrible pain like it's debilitating for a solid minute or two. But she, she as an adult and you know I'm the same way I don't like doctors like I don't like- and part of it's just I'm lazy, I think part of it, it's the same thing she doesn't go and take care of it she just learns to deal with it, right? Versus with my daughter, who's only nine, we're forcing her to deal with it. Right, we're scheduling the appointments for her; we're dealing with everything she's going. She doesn't have a choice. She's getting it taken care of, but for her.

It's more about helping her understand what it's going to be like and what are the realities of living with neurofibromatosis, like, yes, she's going to get those same bumps on her skin and yes she's probably going to have some that have to be removed under the skin, but more than that with her because of the fact that we're treating the gliomas in the brain with the medicine. And for those that don't know selumetinib while it’s a MEK inhibitor it's a form of chemo, right, so she's taking a chemotherapy drug. And what does that mean? like why are we doing it? Explaining everything and explaining the, you know she's a very bright girl and explaining what the risks are and what the options are going to be if it doesn't work it's it's totally different. I don't have to do that with my wife, but you have to handle that very delicately delicately with my daughter.  

Venkata: Totally, I can totally see that. You mentioned how your daughter has a 50-50 chance of getting neurofibromatosis type one and not getting neurofibromatosis type one. How did you deal with the initial diagnosis of your daughter getting NF type 1? Was it easier for you to accept considering your wife was also diagnosed with NF type 1? Was that easier to explain it to your daughter going forward, and grappling with the initial diagnosis?  

Meier: Yeah, for sure. So, a little bit of backstory for us, we tried to have kids for a very long time, and we're not able to, and we ended up having to go do IVF in order to be able to have her, and we were offered the opportunity to say and run some tests on it and say she can have it or not and we opted not to, because in our head, whether she had it or not, it wasn't going to change our mind whether we were going to move forward with the process so we just, we left it up to chance.

And I went into the process with the assumption, she would have it, and so I was able to kind of prepare myself mentally for it, and because I knew what to expect, since my wife had it, it was a lot easier for us to, to prepare him and kind of go in prepared. But then once she actually was diagnosed, which happened at a very young age, we, and as we started to tell her about it and teach it and uh teach her about it as she grew up, we were able to use it, use mom as an example right? She was able to relate with that because it was somebody very close to her. So, I think it's far easier to, to do something like that, when there's somebody close to the, to the daughter that's relatable, like it becomes a relatable disease, she can see what it's like, versus if it was not if nobody in the immediate family had it that would be a lot harder.  

Venkata: Looks like you mentioned some of the preparations you've already taken. If your dah was uh if your daughter was diagnosed with NF1. What are some of the other preparations you took?  

Meier: It was mainly, you know, steeling myself mentally and preparing mentally for the fact that while NF one typically has non-life threatening you know symptoms and side effects, there's always that chance, right, NF1 there's a chance that you're you have a scoliosis style disease, those two are linked together pretty tightly. There's a chance that it's a much more severe case and you know, if you haven't seen it, you've probably heard about the story about Elephant Man, right, who had the massive tumor? That was a fibroma that was neurofibromatosis that caused that. And so just how am I going to think about that and how am I going to deal with that and explain that to her.

And you know there's also, there was also chances that she might have these gliomas in her brain, which she did. And so now we're having to go through that whole process we do quarterly MRIs and we do all sorts of valid, you know, to monitor these things. And I think had I not just gone in expecting this to happen, it would have been much harder for me to be there for her, because we have to be there and be that rock and that support and doing so without it being a surprise I think is a lot easier than just finding it out of the blue.  

Venkata: And many patients with NF1. A lot of parents and patients themselves have questions as to whether or not they should limit their own activities, considering their diagnosis. Could you talk a little bit about that and how if, for that matter, the activities are limited for both your wife, and or your daughter.  

Meier: So we don't we don't limit activities in any way shape or form, we live in as absolutely normal life as we can. My daughter is a very avid softball player. We travel all over the place. The, the only thing that we do with her is we make sure we stay up to date and make sure we're doing the doctor's visits and the monitoring and everything we need to do. I'm lucky in that both my wife and daughter have, on my daughter especially right now. My wife has minimal physical limitations, it hasn't caused the typical kind of deformed growth or bone issues or anything else so she's okay. But where she's limited now is because of her hand. And so she's got very little grip strength and so there's some limitations there that we have to work around but they're just minor tweaks, they're nothing that's life changing or earth shattering.  

Venkata: That's great to hear. Um, you talked about selumetinib. And, could you tell us a little bit more about this drug? And what was your daughter's experience like with this drug in the first month that she was taking it?  

Meier: Yeah, so I'm happy to. So, this story is actually fascinating.  Selumetinib has been in different drug trials now for years and years and years and it has been in an utter failure in every situation it was applied. It's a, it's called an MEK or MEK inhibitor, and the idea there is that it is a less invasive form of chemo, so when most people think of chemo, they think of the chemo courts and the hair loss and everything that comes along with that. This is an oral pill you take it twice a day. The side effects are very minimal, you keep all your hair, though, as it turns out in my daughter's case, she went from a brown-haired girl to a platinum blonde, because it completely de-pigments the hair follicles. So that was again, an interesting side effect.

But, so, AstraZeneca had essentially shelved with this drug, right they had said, okay, it's failed let's move on. And CTF has this amazing little incubator program that they go off to the various pharmaceutical companies and they say hey, we see that you have this failed drug on the shelf and we think it might have a chance at working in this particular scenario and so we'd like to help kickstart some of the research into that space. CTS’s not big, right they're they're from a, from a financing and a pharmaceutical perspective they're tiny right but what they can do is they can build those bridges and fund those, those kind of angel almost like an angel investing exploration to get data that will then convince the bigger players to actually put more money behind it and that's that's the story of kind of what happened with selumetinib.

And so they started doing trials specifically on non-plexiform gliomas, which are the ones- glioma is technically a form of cancer by definition, but it doesn't self-replicate, so it's not your typical what you think of when you think of cancer, and so they brought it out and they said okay well let's start some clinical trials on on this specific form of a glioma greater than 90% success rate and shrinking the gliomas like this drug that had been in the eye of the beholder a complete and utter failure is now a undeniable success in a very niche market. And so, and that would have never happened I believe without CTS kind of prodding and involving and the relationship they built with AstraZeneca in the past two, so that was big.

So it was FDA approved last April. My daughter started taking it in September. And ever since then, the medicine’s been doing exactly what we hope to do which is to kind of keep the gliomas the same size don't shrink them, and the side effects have been minimal, and like I mentioned the hair, but aside from that, other than having to adjust the schedule around only being able to eat at certain times or having to wait so long it's been straight on forward nothing's really changed, which is fantastic when you think about the fact that it's a considered a failed drug, right?  Meier: Yeah, so when you think about selumetinib in general if you look at the side effects they're really really minor, especially in this age group.

So ingrown toenails, oddly, are one of the side effects; mouth sores, dry skin, and the lightning of the hair, are about- that's about it. And for my daughter's case, she had a little bit of dry skin, but it was, it was in the face area so we weren’t sure whether or not it was from mask rash. No thanks to COVID, everyone's wearing masks, it was hot and humid, so we weren't sure if that was the cause or not but it was super minor. She didn't have any of the mouth sores or any of the ingrown toenails but her hair is completely blonde, so that was the biggest side effect of her.  

Venkata: Could you talk a little bit more about your daughter's initial diagnosis that led to her taking selumetinib, you mentioned that had gliomas in the brain was an incidental finding or was it something that was only brought up after a symptom that manifested itself?  

Meier: Yeah, so it was 100% an incidental finding. When she was born she had this bump over her eye. And so, we took her in and the doctors like look, it's probably just a cyst, don't worry about it. Wait until she's a little bit older, so she would have waited until she was two, two and a half. And we took her in to a dermatologist just to have it looked at, and she goes, well, let's just get an MRI and make sure it's a cyst, and then we can be sure from there and so she was two and a half, three whatever she was at the time, an MRI of the head meant putting her under and so she went under anesthesia for the first time.

They did the MRI and yeah it was just a cyst, but at the same time they found a glioma in her optic nerve. And so our, our, our ophthalmologist had basically said, it’s normal with NF patients. Don't worry about it; we'll do yearly eye exams, and my wife called me up freaking out at work because she Googled it. The worst thing you can ever do is Google disease right? well, you're all- everyone's dying when you google this thing on Web MD right? And so, we called around and we found a neurofibromatosis expert in the, so we live in the Bay Area, and so down in Stanford and it just so happened that she was a neuro-oncologist with an expertise in neurofibromatosis which is bizarre and so we wanted to go see her. And she goes, yes, it's normal, but let's monitor it, so we kept monitoring it.

We started with quarterly MRIs, we went to six months, and then we did yearly. And after the first yearly MRI, we found a second glioma, so this entire time the one on her I had stayed completely stable and was causing no issues. We found a second one that was located near her brainstem, where the, the brain the the CSF the blood brain fluid essentially where it goes from the brain down to the spine and then releases out to keep the pressure down. It was growing right there and she says, Okay, we need to keep an eye on that, so we went back to quarterly. So we kept an eye on it over time and it just kept growing, a little bit at a time and a little bit at a time. And so, we started talking about what were the treatment options because of where it's located surgery wasn't an option. Radiation isn't really an option there.

And so the only options were either a selumetinib which at that point hadn't been approved yet, or a shunt, right, because the concern is as that glioma grows and impinges on that valve right it would prevent the fluid from being able to leave the brain and cause a swelling in the brain which can cause all sorts of problems. And so we, we kept an eye on it, we were on track, and then one day, it grew just enough to where you could start to see a very slow impingement of that valve and so we decided to proactively move into the medicine phase because it had been approved at that point. But if for some reason this medicine doesn't work, which we won't know for another year and a half or so, whether or not it's actually effective. We would have to move to put a brain shift and to make sure that the brain fluid could still flow.  

Venkata: So you mentioned how selumetinib was just approved when your daughter was put on this medication.  

Meier: Yes.  

Venkata: So it's been a little over a year since your daughter has been taking his medication.  

Meier: A little under, so selumetinib that was approved in April. She started the medication in September. And, so we just had our nine month checkup on the with the medication, and so far everything is stable, it's not growing anymore, which is about the best we could hope for because selumetinib actually requires 10 months in the body to reach full efficacy. At that point it should actually start being able to shrink the glioma is that, so hope we're hopeful for our next scan in September, because that will be a year mark that maybe we might see some shrinkage.  

Venkata: Could you tell us a little bit more about selumetinib and your daughter's experience in the sense that you told us so far you mentioned how her only real side effects were the changing of her hair color. Has anything else noticeable happened since the first month till the ninth month?  

Meier: No, actually, so we are incredibly lucky that she has been asymptomatic the entire time. We, in reality, had we not had that cyst on her eye looked at, we probably would have no idea, any of this was in place, we would just be kind of blissfully going on, but I think that it's a good thing that we found it right it's a good thing we're treating it. But she's, luckily, been asymptomatic and so you know we do watch for a few things she does occasionally, well, randomly throw up after either exertion or laying down and that is a sign of hydrocephalus. And so, we have to be cognizant of that and make sure that doesn't start increasing but I think really, that's probably the only noticeable change in the last nine months is maybe, maybe a little more frequent random vomiting, but nothing, nothing that's worried us or the doctors yet.  

Venkata: I'm really glad that selumetinib is doing its job, it seems, and the progression or the growth of the glioma at the brainstem, at least for now, has stabilized, and maybe in the future might even shrink. It really attests to the importance of screening, and the importance of, like you said, CTF going around and being able to look at these drugs and giving them a second chance.  

Meier: There are so many failed, drugs, sitting on pharmaceutical companies vaults that if they were looked at my favorite story and I'm gonna I might get this wrong so don't quote me on it, but that Viagra actually started off as an Alzheimer's drug, right, and that was what it was originally trialed for and obviously it was a failure there but they found something that it is good for right? And so, there's a lot of these things where, when a drug is developed for one situation, and it doesn't work, don't throw it away. Right? Let's send it out there and see if we can continue funding these small alternative trials and saying there's a chance that it might be able to impact this. The human body is ridiculous. It is so- it's such an amazing piece of architecture, and we're only just now starting to understand it, so there's no possible way that we can know for a fact that these failed drugs don't have applications in other places.  

Venkata: No, I completely agree. And so far we talked about your experiences, describing someone with both your wife and your daughter who both have NF1? But I'm curious, as a caregiver of someone who has NF1, how has it affected your life?  

Meier: So, I am incredibly lucky that the program that we do at Stanford Children's Hospital, they manage a lot of the complexities around the different scheduling, because every time we go in for an in-person appointment now, we're doing an MRI, an EKG, an EEG, a visit with the doctor, blood draws, all of these things are at the hospital and they're all scheduled independently. And so, it can be a pain to work with the various providers to schedule. They do their bestkeep me out of it but that's definitely part of it. Part of it is dealing with insurance too. And again, I feel like I'm incredibly lucky because selumetinib is a $10,000 a month drug right now. And it's so new, and there's no generics for it. So, the assumption would be that we were going to have to fight it for our insurance company, but I really want to call a shout out to AstraZeneca here so not only did my insurance company just automatically accept it no questions asked approved on the first time which is unheard of.

But AstraZeneca even or Stanford Children's rather automatically applied us enrolled us in the copay forgiveness program that AstraZeneca has and we were accepted so we literally pay zero cents out of pocket for this thing, every single month, which is such a blessing when you consider, you know where we would be without it. And so, I know that the pharmaceutical companies and the insurance companies they get a bad rap and some of it is justifiable, but there's also a lot of really good things they do. And so, I think for me what's changed is my life as the caregiver is, I am intimately familiar with the phone tree at many different doctors’ offices now. But on top of that, I have a different viewpoint into into pharmaceutical companies and into insurance companies that I may not have had before, because I've had the opportunity to have good experiences with it. And so, for me it's kind of just broadened my horizons I used to hate pharmaceutical companies right and insurance companies were just a pain we had to have, but once you rely on them? It's a different viewpoint.  

Venkata: No, that's amazing. Do you have any other advice for caregivers like yourself who are in your position, or who might be in your position in the future?  Meier: Yeah. Two things, educate yourself. It's a lot easier for you to be able to do the necessary things when you're caregiving, especially when it's for children, right? When you understand at least from a conceptual perspective what they're going for through right? You're never going to be able to say oh I know what you're going through because you know you won't. Right, but to be able to at least speak intelligently with them and talk about them at the right level it's really important, so absolutely whatever it is, whether it's NF or anything else just educate yourself if you're a caretaker.

And secondly, just because you're a caretaker doesn't mean you don't have your own needs. So, make sure that you're taking care of yourself that you're giving yourself the breaks that you need, that you're you know you're doing whatever it needs to keep you in the best mental and physical place that you can be, because you have other people depending on you and so you need to make sure you're taking care of yourself.  

Venkata: Mr. Meier, thank you so much for being on our podcast I think that's really beneficial advice, and I'm so glad that we were able to have you on.  

Meier: It was my pleasure. This is a tough topic to talk about. Not a lot of people know a lot about it and so it can be really hard to find the information so anywhere that I can do to help I'm happy to.  

Venkata: Thank you again.  

Meier: Absolutely. Have a good night.