Genetic Disorders of the Eye: Living with Vision Loss, Patient Advocacy, and Rare Disease Research
Dasha: Welcome to the Biomedical Frontiers Podcast, where we explore pivotal research projects and disruptive innovations aimed at translating scientific advancements into tangible healthcare solutions. I'm your host, Dasha Tyshlek.
HIGHLIGHT REEL
 As the disease progresses, it starts to remove things from your list of capabilities. I reached a point where I can no longer safely take care of patients. I reached a point where I, I couldn't drive, and now I'm at the point where I can't safely navigate the world around me.
 One of the issues that a lot of my patients run into is that there's not affordable, transportation for them. A lot of patients fall into a gap where they don't qualify for disability because they're not legally blind, but their vision's not good enough to drive.
 What does it change to have the right diagnosis?
 Simply having an answer and getting a diagnosis and knowing what you're dealing with is important. Many patients, as they go through their diagnostic journey,  they struggle to understand what's happening to them. That journey, which can take several years, can be very difficult and frustrating.
Abby: I'm Dr. Abby Fahim, 
Chris: I'm Chris Moen, 
Abby: and today you will learn about cutting edge research in  Choroideremia and other inherited diseases of the eye. 
Chris: You'll learn about living with vision loss and being a patient with a rare disease 
Abby: and how we hope to translate discoveries from the lab into treatments for these patients.
Dasha: Abby and Chris, welcome to the show.
First and foremost, I wanna make sure we understand what is choroideremia, what causes it, and how does it affect vision. Dr. Fahim, could you start us off with an overview? 
Abby: Yeah, absolutely. Choroideremia is one of many inherited retinal degenerations, so these are types of diseases where there's a mutation and a particular gene that leads to the.
Photoreceptors or the cells that line the back of the eye that send light and send vision to the brain, it causes these cells to not work properly and slowly over time they degenerate and the patients slowly and progressively lose vision. So choroideremia is one of those diseases and it starts with loss of rods, which are responsible for our night vision and a lot of our side vision.
So patients have night blindness. They have loss of peripheral side vision, and over time they can develop tunnel vision where the central vision is good, but it's like they're looking through a tunnel and this makes it really hard for them to navigate in public, drive a car do a lot of the things that we take for granted.
And unfortunately, this disease affects people fairly early in life so they can be legally blind by early adulthood. 
Dasha: And you said this is inherited, is it any time that it's inherited, it happens or does something activate it? How does the inheritance piece of that work? 
Abby: Yeah, so some, I mean, some diseases, you're right.
Just having a disease causing mutation doesn't necessarily mean you'll develop the disease, but in this case, it has 100% penetrance. Meaning if you have the mutation, you get the disease. With one caveat, it is X-linked. The gene is on the X chromosome. So males tend to be affected or al, they're always affected if they have the mutation because they only have one copy of the gene.
One X chromosome. Females have two x chromosomes, so their normal copy makes up the difference and they usually aren't affected, but occasionally can be. 
Dasha: And you also mentioned that it can affect a person starting at an early age. Is anything determining how early the disease starts to become evident?
Abby: Yeah. You know, we can detect the changes on imaging by the time a child is in grade school. But they're not always, they don't always come to clinical attention that early. If there's no family history and they're, they're not aware that this disease runs in their family, they may not come to attention until adolescence, even though they've been having some retinal degeneration already for some time.
Dasha: Yeah. Chris, you are a patient advocate, but you are also a patient yourself, so you have a deeply personal story. Can you share what is the progression of choroideremia like for a patient? What is the patient really experience and, and then the challenges in getting diagnosed and getting treated. 
Chris: Well,
I'll start by outlining the progression of symptoms maybe. And then get into some of the impact that of, of the disease as you described. So most people keep in mind there's some variability and progression, but most people will start like I did with night vision issues in their childhood. I, for one, found out about my diagnosis when I was 12.
So in my childhood, I just assumed I was normal and that everybody had the challenges that I did. But as I got into my teenage years and, and again found out. My diagnosis, the development of blind spots in my peripheral vision started to be more of a problem. I still had, you know, relatively normal life experience, I would say.
I mean, I did well in school. I drove a car, I played sports. But those blind spots continue to get larger and coalescent eventually will make a ring of blindness around your central vision or what commonly is referred to as tunnel vision. I reached that point probably into my twenties and thirties, and it's at that point that it started to have much more of an impact on things like my mobility my independence.
I had to stop driving and eventually start using a mobility cane. And I would say most patients with choroideremia lose all of their peripheral vision by about the twenties and thirties. As vision continues to progress you, you know, develop. I should say your visual field becomes smaller and smaller.
Your tunnel becomes smaller and smaller, which impacts a lot of things in your life. It impacts your safety as things that you might notice walking down the street or through a busy city are very dangerous to me. Up and down stairs, curbs, tree roots on the sidewalk and such. As well, the challenges with night vision and bright sunlight become more difficult, so there's big bigger issues going from dark to light spaces and vice versa.
There's more challenges with brightness and glare, and then inevitably as that small tunnel shrinks. Even further and eventually closes all together I'll start to develop more and more difficulty reading, identifying faces and people, and eventually will lose all my sight, which typically happens in the sixth or seventh decade of life.
So you can imagine living with a disease like this is very challenging. You know, you start off with your life being just like everybody else and being able to do normal things. And as you mentioned, I, you know. Went to college in medical school, and I practiced as an emergency physician for several years.
But as the disease progresses, it starts to remove things from your list of capabilities. I re I reached a point where I can no longer safely take care of patients. I reached a point again where I, I couldn't drive, and now I'm at the point where I can't safely navigate the world around me. Even with using a a white cane, I oftentimes need assistance with things.
It's difficult to read you know, things that come normal or. Easy to, to those of you with sight are oftentimes extremely challenging or sometimes insurmountable with with severe vision loss and blindness. You know, there are some technologies that help. Certainly smartphones are a big, a big assistant and, and there are things coming out on a fairly regular basis, but it's certainly very challenging.
There's a lot of, you know, mental health issues that come with having blindness. And I think I. You know, I'm, I'm at a point where I, I kind of developed ways of dealing with the progression of, of light, of sight and loss, but it can be very difficult for people. You asked about the diagnostic journey.
Choroideremia is a rare disease, and, and for all rare diseases there is, there tends to be a delay in diagnosis and oftentimes misdiagnosis, most patients will initially typically be diagnosed with a more common, retinal degenerative disease, something, typically a Retin that is pigmentosa or RP is typically the first diagnosis, and that was my case.
And as the disease progresses and starts to change in morphology a bit an astute clinician may notice some changes or may recommend genetic testing for an individual which is inevitably what patients will need to have, to have confirmation of choroideremia. Like that genetic testing isn't covered by insurance and could be rather expensive, so it may not be something someone wants to do.
But is is really, you know, the only way to sort of confirm that that is in fact the disease that an individual has. 
Dasha: What does it change to have the right diagnosis?
Especially given that you are saying it's not even typically covered by insurance and, and expensive and not everybody's gonna be recommended that. 
Chris: I, I'll jump in first. Abby. I think Sure. Number one, simply having an answer and getting a diagnosis and knowing what you're dealing with is important. For many patients as they go through their diagnostic journey, they struggle with the
inability to understand what's happening to them. And, and that path, that journey, which can take several years, can be very difficult and frustrating. So simply just knowing, even if there's nothing you can do, knowing that this is what I have, I can educate myself on it and prepare myself on it, is, is really important.
Secondarily, from the research side, again, there are no treatments for choroideremia nor are there for most of inherited retinal diseases. But knowing what diagnosis you have can support the research efforts. So it can help with the development of natural history studies where scientists are able to get a better understanding of the progression of the disease and use a number of different diagnostic modalities to look at the retina.
And certainly if and when there are treatments. Is being tested in clinical trials. Genetic testing is mandatory to confirm that you actually have the disease that you think you have so that you can enroll in those clinical trials. So it is really important even if there's not an available treatment.
Today for, for that patient. 
Abby: I agree with all of those points, and I'll say that there, there does tend to be a difference between our pediatric patients and our adult patients in this respect. Parents always wanna get genetic testing for their child. I, I've never had parents say, no, I, I don't wanna do the genetic testing.
But adult patients will, will sometimes say that, you know, sometimes they don't necessarily care to have that definite diagnosis. Whereas other, other patients really do. It really depends on the patient. But the reasons that we recommend genetic testing are similar to, to what Chris outlined. I tell my patients: number one, it can help you know risk to family members. Number two, some of these genes have other systemic manifestations that your primary care doctor would wanna be looking at. You know, some genes affect heart, kidneys, other things. And number three, as Chris mentioned, there are clinical trials.
And in fact there have been clinical trials for choroideremia. So in, in particular, when a patient looks like they have a disease where some of the genes are known to have clinical trials then I encourage them to get genetic testing to know if they might qualify for one of those trials. And finally, and I'm very passionate about this, and Chris hit it on the head, you know, the more that we
say genetic testing's that important, 'cause there's nothing we can do, the more it becomes a self-fulfilling prophecy. Because , in order for sponsors to be interested in a disease, to develop treatments, there has to be a critical mass of well characterized patients.
Getting those patient genetic test results and, and getting them out there and in the databases is really helpful. And we do, there are, there are some no cost options currently for genetic testing depending on the, the patient, so. 
Dasha: Abby, you're also an assistant professor of ophthalmology and visual sciences, practicing doctor at University of Michigan Medical School, and you're leading some of this research yourself.
So can you tell us a little bit about, what is the research in Choroideremia? And then what kind of the future of your research might yield for this patient population? 
Abby: Yeah, absolutely. Choroideremia is a special research interest of mine and there has actually been a lot of research progress over the years in terms of our understanding of the disease.
Even translating those discoveries into treatments, you know, in one sense, you know, we still don't have any FDA approved treatments. And so in one sense it doesn't matter till you actually have a treatment that you can offer to the patient. But in another sense, all of these discoveries that we make are getting us closer, to a treatment. The only question is when, and we really just don't know there will be a treatment one day. I wish we knew when but there's been so much research and there have been a couple of gene therapy clinical trials already, unfortunately not successful to the point of getting FDA approval to actually be able to offer that to patients.
But my work is primarily in the lab looking at the mechanisms. At the cellular level of why the retina degenerates so that we can identify new pathways where we can intervene to treat the disease. So we've known about the gene that causes choroideremia for a long time. It's called the CHM gene, and we've known what it does for a long time.
It's really important for a process called RAB penetration. So RABs are these small proteins that are responsible for shuttling other proteins around the cell. They're like the bus drivers of the cell. They get the other proteins where they need to go. And, and when you have. A choroideremia gene mutation, these RAB proteins don't work properly. And so as you can imagine, that would have a lot of downstream consequences. And in our lab, we've discovered a couple of those consequences. One is the cells have increased signaling of mTOR. mTOR is a master metabolic regulator, and as a result of this, the cells have reduced autophagy.
Now that's autophagy is a word that's been kind of a buzzword in some of the popular media lately. If you read any like anti-aging articles or Fountain of youth articles, autophagy is a way that cells cope with stress. By digesting old damaged proteins and organelles and parts. And so it's like a way for cells to rejuvenate.
And so you can imagine if cells can't do autophagy that that's gonna be a problem for the cells. And the other thing we discovered is that the cells secrete more proteases and proteases are these like molecular scissors that cut up the scaffolding that hold cells together. And so we think that that really might be important for the severe.
Atrophy or loss of the choroid, which is the blood supply that feeds the retina, and that's how Choroideremia gets its name. So these are all things that we're investigating further. It's not that we have a treatment already that we're developing, but these are all discoveries that we hope can, in the future, translate into a, a treatment.
Dasha: So just to kind of explore that a little bit, understand it a little bit better. I hear you saying that there's multiple mechanisms happening at the same time that could be impacting exacerbating or working off of each other.
Abby: There's like over 70 known RAB proteins. They direct traffic in the cell and so they determine, they shuttle around the other proteins to the, compartments they need to go to. And so the RABs aren't functioning properly in this disease, that's actually been known for a long time. What's been unknown is what are like, what are the downstream consequences of that that lead to retinal degeneration?
And so we've found a couple of downstream consequences. The hard part is knowing which, which of these are relevant for the disease. And so that's the further investigation we're doing with cell culture and mouse models to, to try to figure out what's most important for the disease. 
Dasha: But the building blocks that you describe, I mean the mTOR and the autophagy, these are processes that are present in all cells, not just retinal cells.
Yes. And all cells of the body. So one of the things I heard you say is one of the reasons important to really nail down the diagnosis and do the genetic testing is if there's other consequences to other places in the body, not, you know, maybe that are less obvious. Yeah. Can you speak a little bit about those relationships and, and what, what the research is finding about that?
Abby: Yeah, that's very interesting for you to bring up. So, choroideremia is really not thought to affect other parts of the body. There has been some reports of maybe some altered cholesterol and lipid levels, but it really hasn't really not to the level of being proven. And certainly, you know, patients with choroideremia aren't known to have,
increased rates of high cholesterol or anything like that. And that's really one of the interesting questions in research. You know, these RAB proteins are important all over the body. And the CHM gene is expressed all over the body. Why is the disease only in the eyes? And there's some high hypotheses about that, which are somewhat complicated, but suffice it to say there's some redundant mechanisms built in that may be more prevalent in other parts of the body compared to the eye. And also as I mentioned before, there are over 70 known RABs. They're not all going to be as important in every type of tissue.
And so part of our research has been looking at which RABs are most dysfunctional in the retina cells compared to the rest of the body? 
Dasha: Okay. Well, Chris, you have had a lot of experience in kind of a chief medical director, chief medical officer role working with the Choroideremia Research Foundation, so you're getting this broad view of the research, I'm guessing even globally.
Could you share a little bit about what you're seeing in terms of collaborations, partnerships, and kind of new ideas that should give people hope and give them something to think about in terms of where the research might be headed next on a kind of massive scale? 
Chris: Sure. And I maybe would start by talking a bit about the genesis of the organization back in 2000. At a time when there was very little research being done on Choroideremia and comparatively very little known, so a number of individuals like myself who were affected by the disease, met each other on the internet and decided to start a 501c3 to help raise funds to support more research. I got involved several years later in 2008 took over as president of the organization.
From 2014 to 19, and since then served as the Chief Medical Officer. The focus of our organization, first and foremost, is to support research. At that time, we were supporting, initially supporting one scientist who was. Potentially working towards and eventually did successfully develop a gene therapy, as Abby described that, that that was in clinical trials, although didn't make it all the way through.
As we've grown in size and grown in fundraising, we now raise several hundred thousand dollars a year and can put that, that funding towards a number of different researchers who are doing a number of different things, either as Abby described. Understanding the basic mechanisms of the disease better or potentially towards, directly towards new treatments that may be in the laboratory, and trying to bring those in into the clinic.
That work requires. Some effort to understand who the scientists are, right? Who, who might be interested in working on the disease or who may be working on something similar that could be applied to Choroideremia. And so we spend a lot of time kinda canvassing the research sphere to understand who, who the right people might be and what research is currently being done that that potentially could be applied.
To Choroideremia. So that involves using, using the internet, it involves going to scientific meetings and conferences where scientists like Abby will be and maybe presenting their research to go meet them in person, you know, learn about what they're doing and maybe sell them a bit on, on us as a patient population and us as, as a disease target.
We also interface and work with a number of pharmaceutical companies who've either have. Previously run clinical trials for emia or who are potentially pursuing a medication that could be beneficial towards patient with our disease. Lastly, you mentioned sort of collaborations that's that's.
Something that's become really important to us as an organization that doesn't raise a lot of money. We, we simply can't afford to fund multiple scientists who are doing the same work. So it's really important to bring the scientists together to help share what they've learned and maybe collaborate on projects.
And we've been successful in that over the years. Having, we've had a few individual scientific symposia where we invite scientists to a, you know, to a single location to present on their research and talk about potentially interesting concepts moving forward. We also developed an inter, what, what's called, what we call the ICRN or the International Choroid Re Choroideremia Research Network, which is in sort of a virtual meeting room for scientists that meets periodically across the globe and can kind of share updates.
And help us as an organization understand how the landscape changes and where we might eventually pursue future projects. So it's, it's been, it's been a long road and, you know, while we don't have a treatment, we're, you know, very proud of the work that we've done in 25 years, moving from a time where no one even knew what EMIA was, let alone was interested to a time when it, it's, it, you know, there's multiple funded research projects in the United States and around the world many of which.
Funded by our organization. 
Dasha: I heard both of you mention that several gene therapy treatments have been attempted at this, you know, obviously early stages. It's very difficult to develop a new drug that's successful and. If you have a small patient population and not a lot of underlying research yet, or not, not the baseline that you might want to see, it can be more difficult.
Would either of you be able to kind of comment on the gene therapies that have been attempted? First of all, what is gene therapy? Why is that the, the methodology for, for drug discovery that's been pursued for choroideremia? Then also what's been learned from these trials if, if they weren't successful at developing a treatment or at least passing FDA, what has been learned from that experience?
Abby: So gene therapy can mean a lot of things, but and it's, it's most common form. It's call, it's gene augmentation or gene replacement. So it's been used most commonly for. We call autosomal recessive conditions. In this case, X-linked recessive, meaning that basically in these diseases, the mutation in the gene leads to a loss of function of the gene.
If you can give the cells a normal copy of the gene, in theory, they should be able to work properly and survive. And so gene therapy provides a normal copy of the gene packaged into a viral vector and viral particle. We use adeno-associated virus. It's a safe. Virus particle to give to the body. And it's injected under the retina in a surgery.
It's an eye surgery and, and the virus particles are suspended in a fluid that gets injected under the retina and the virus essentially infects the retina cells. It as viruses do. It attaches to the retina cells and inserts its normal copy of DNA into the retina cells so that they can make a normal copy of the gene.
Hopefully function well and survive just as though they never had the mutation. And so that's, that's the idea. And the reason why this method has been chosen is 'cause it's been successful before in a retinal disease which, was the first FDA approved gene therapy for any disease. And that was in 2018.
And that's LTER or Tigen. Parva, which is a gene therapy for RPE 65, which causes an early onset form of blindness. And so that that was in a sense wildly successful 'cause the patients actually. Tend to improve in their vision. In particular vision, in, in dim, dim lighting. And so there's been a huge interest in gene therapy and retinal gene therapy.
Since then, every retinal disease is different and for a lot of retinal diseases because of the mechanism of disease, we don't necessarily expect gene therapy to improve vision. We're just hoping it'll slow down progression or hopefully stop progression. And that's probably the case for choroideremia.
But these clinical trials and sponsors are somewhat limited in the endpoints that they can use to get approval from the FDA. And in this case, the trials, we're trying to use an improvement in visual acuity as their endpoint which is probably not a realistic endpoint for choroideremia. So that's one of the major factors that, in my opinion led to, it's possible that the gene therapy worked.
But if you're using that as your. As your endpoint it's probably not gonna show anything. 
Dasha: And, and just to clarify, it could have been slowing like disease progression. Yes. 
Abby: Okay. Absolutely. Just 'cause it didn't improve Visual acuity didn't, doesn't mean it didn't work to slow disease progression, but the trial wasn't set up to look at slowing of disease progression.
Dasha: And, you know, clinical trials I know are very expensive to run and there's probably some unique challenges for running a trial in a very, in a smaller population. So maybe Chris, we can talk a little bit about what those challenges are and how do you even set up one of these trials for a rare disease like emia?
Chris: Absolutely, and we, we've worked with several different pharmaceutical companies as a partner, I would say, of sorts in these clinical trials. And one of the. One of the difficulties, one of the struggles for investigators is finding patients choroideremia. For example, we estimate has about five or 6,000 affected people in the United States.
Our organization has, you can through its membership. I think we, we know about a thousand that exists. So there has to be a way that, that the company can identify who those patients are, and certainly they're trying to identify patients with particular. Characteristics, not all patients. So it can be difficult to find the population that they, that they want to treat.
And as, as the, as the trial size gets larger, obviously that becomes more and more difficult. Secondarily as I mentioned before about natural history studies there, there haven't, we sort of understand the progression of choroideremia, but up until these clinical trials started, there were no. Call them scientific, natural history studies to kind of formalize the process and the, the, the progression of the disease.
So those had to be completed as well, which. As you mentioned, very time consuming and costly, and certainly, you know, pharmaceutical companies are their industry, right? They need to be able to see some opportunity to, to, or to get back the funds that they put into the research and development phase. And so there needs to be an opportunity to treat additional patients if and when you do get a drug that's approved by the FTA our.
Disease is rare, but not ultra rare. Some populations of patients, some, some diseases, you may only have 50 patients or a hundred patients in the country or the world with that particular disease. And so your clinical trial will literally consume the entire treatment population. So it can be very challenging for sponsors and that really some of that puts the onus on us to be able to help them understand how we can help, how we can identify with enrollment, how we can give guidance on.
Things like the clinical endpoints that Abby talked about to, to help sponsors understand what endpoints might be really relevant to our disease and what endpoints like visual acuity improvement probably isn't really, I. Isn't really likely to be a useful endpoint. Sometimes they, they take our information and put it to use and sometimes they decide to go a different direction as, as they did in, in, in, in these trials.
But that partnership is really, I think, critical for both, for the, the pharmaceutical company and for the patients to be able to have some voice in the development of that clinical trial process. 
Dasha: You mentioned a few numbers as low as 50, as low as a hundred patients. What is exactly the bounds of what makes something a rare disease?
Chris: There can be different definitions depending upon what what you look at. I think the general consensus is that less than 200,000 patients is considered a rare disease, which gives you a quite a far range of, of of patient populations. Some diseases are referred to as ultra rare, and there's not.
And Abby, correct me if I'm wrong, but I don't think there's a specific number necessarily. I don't 
Abby: think so either. 
Chris: Yeah. But, but certainly I think we would all agree that if there's, you know, double or, or triple digit. Patients in the US or internationally in a particular disease. I think we'd all agree that's pretty rare.
So, 
Dasha: and that 200,000 is, is in the US or globally? 
Chris: I think that's the United States. 
Dasha: So when you look globally, there could be a larger population potentially. And it's complex. It's also 
Abby: complex 'cause not every country has good access to genetic testing. So they're probably large populations of undiagnosed patients that we have no idea exist or where they are.
Dasha: Yeah. And for our audience, I just wanna call out in the same season that, that we're doing right now where we're focusing on physicians who are leading innovation. We're gonna actually also do an episode on nano rare diseases a few months from now. So for those of you who are interested in those, ultra nano rare on what happens when you get into patient populations of one to.
A 10 or one to 50. We'll also be doing a segment on that. So make sure you check out the next episodes so that you can learn about that as well. But going back to rare diseases where those are small, but there's still more, it's more than one individual or two individuals. I. So, Chris, you mentioned you guys have like, almost like a pitch that you do a way to, to really speak to the pharmaceutical companies, the research groups to, to con, you know, to convince them why there, there is reason for them to pursue.
What have you seen in terms of, can you deliver some of that pitch? And then also could you talk a little bit about the response and some of the different ways that you're able to broker relationships so that. Obviously something where you could run out of, of you know, having enough patients to sell something to, to be profitable.
How do you navigate that and figure out ways to still make it worthwhile where there is a monetary interest from, from companies? 
Chris: Some of that pitch is just sort of interpersonal of. Having people get to know you, get to know what you deal with, what your challenges are, and the drive that you and your organization have towards developing a treatment.
I think, I think even in this day and age of sort of virtual and remote life and social media, there's still value in power and face-to-face meetings and, you know, getting to know people. So I, that that's a piece of it, but there certainly needs to be more than that, right? So data's really important, I think being able to present a patient population.
To, to a, a potential investigator, whether they're an academic in investigator or a pharmaceutical company is really important as well. Being able to provide them with additional data about the disease and the expertise that we have about the disease helps them. You know, oftentimes, particularly when we talk about pharmaceutical companies, these aren't the, the, the people running the trials may not be the experts in the disease, but they're the experts in pharmaceutical development, in clinical trial management.
So they are, they rely on. Data that's provided to them in many ways of, you know, on, on the disease and the characteristics of it. So what we often do is we, we can, as I mentioned before, the natural history studies that we help to push forward. Those are now publicly available so we can direct them to that information and help them to understand the disease progression.
We also are connected with. Experts in what we call key opinion leaders in Choroideremia and so can help these companies identify who those experts are so that they can have some, some research and clinical scientific advisors to help them in in their. Platform development. So I think those are really big pieces.
You know, there are other diseases where they may not have that in play or maybe they don't have the knowledge of things like the, the disease progression or the natural history or the mechanisms of disease, and it can be a little bit challenging at times to make that pitch. 
Dasha: I. One of the things that I take away is that through this patient advocacy that you've been doing, and through the scientific community advocacy and the partnerships, and having you as a, as a medical officer in the group and, and digesting the research, you're able to offer a kind of personal partnership because it's a smaller group, you know, rather than like all the diabetes in the world.
Like there's much, you know, there's so much more you are able to offer something like. We can be your guides, we can be work with you really one-on-one, might not have all the resources or as many people, but because we're small, we're more agile, we're more informed. We have that handholding relationship.
We can sit down with you in person rather than virtually. And that's almost like a value in and in and of itself that you're able to, to share with both the researchers and the companies. 
Chris: We believe it is one. One of our, one of our former leaders of the organization once said, you know, with. Diseases like diabetes and hypertension, you'll hear people say, oh, well they're going to take care of it.
They're gonna find better treatments, they're gonna fix my problem. And in rare disease, there is no thing the the people that are going to fix the problem are the population with the disease. Most scientists and clinicians don't even know the choroideremia exists, let alone no information about it. So it's incumbent upon the people with the disease to kind of push.
For research to push, for treatments to raise their hand and say, Hey, I'm here. I exist and I need your help. And so that I think is, you know, empowering for us to know that we can make a difference and we can look back and see the difference that we've made as an organization by how, how much advancement has occurred over the, over the last 25 years.
You know, as for the financial piece of it, I, I mean, I, I don't disagree, right. I. We want to have treatments that are affordable and available to people, whether in the United States or worldwide. I, as a patient advocate, don't have much control over that. So my goal is how do we help scientists like Abby find ways of treating this disease?
And then how do we help that company that may want to then take it into the clinic to accelerate that process as much as possible to try to make it as effective as possible, and to design that clinical trial so that at the end of the trial. If the treatment works, we can get an FDA approval, you know, the cost and the financial piece is really not up to us, right.
That then becomes be between the, the pharmaceutical industry, the insurance industry, and the like, to kind of figure those details out. But at the end of the day, what we want to do is pour gasoline on the clinical development process so that we can get from. Where we are now to a treatment as quickly as possible, and that's a victory for us.
Dasha: I have a kind of a, it's a multi-pronged question, but there's a few really interesting technologies, including ones we spoke about on this podcast, like AI driven drug development. I. And not just, you know, not just things that do digital twins, but also things that then like, take a look at like what the disease is and make suggestions for the drug development path.
And then make manufacturing of that of specific proteins, like really simple, like basically AI builds the protein that you need. One technology. Another is more of a political kind of issue going on right now, which is, I don't know if you saw the lawsuit against like Nature and Xavier the five biggest science publication companies for basically it's an antitrust lawsuit saying that they, you know, they basically, I.
Lock up research, get everybody's money, which is all mostly govern government money or private foundation money and make everybody pay for access and, and basically stifle research and innovation in that way. And, and then, you know, we have generally like this, this kind of discovery of information online, AI kind of proliferating how, how easily you can research and find information, digest things like scientific papers.
Do you see any of these technologies having a particular impact on rare disease research and also rare disease sort of patient learning and education and, and doctor education? And if so, do you, what do you see kind of potential future directions that could be taken with such technologies? More we're thinking more like, you know, outside the box, like big picture.
Not necessarily something that's happening today, but. 
Abby: Yeah, thus far, I, I would say it really hasn't had a big impact on rare disease research, to my knowledge. More of an impact on the more common diseases. You know, one of the things about AI and learning algorithms is that it requires a large amount of data, which is obviously easier for, for more common diseases.
So that presents a challenge when using it for rare disease. You know, I have seen some proposed research projects looking at, like, it's more diagnostics, you know, looking at imaging for rare diseases. Again, with the challenge that it's, there's not as much data as the more common ones, but in terms of translating into therapies, I really haven't seen AI have an impact yet.
Chris: I would agree with that. And specifically for, for our disease. We, we did have a, a study several years ago, probably in the earlier phases of ai, that that part of the study was particularly focused on testing different, currently available FDA approved drugs on a, on a zebrafish animal model. But there was also some of what you described of computer modeling and, and, and AI to try to identify if certain compounds could potentially be beneficial to the disease and it.
Long story short, it wasn't, wasn't effective. It doesn't mean that it couldn't be effective for other diseases, but as Abby described, the more you know about a disease process, the better AI potential there is to identify an avenue or a target to, to apply a treatment. So I think, you know, we're in a, a revolutionary age right now with, with ai and it gets applied to so many different things.
So there's, there's definitely, I think. Some potential down the road. I'm just not sure that it's as clear today as it might be in say, five or 10 years for, again, specifically to rare disease. 
Dasha: It's very interesting. I, I hadn't thought about the, the issue of quantity of information, but that makes a lot of sense.
Well, I wanna turn from the specific disease of choroideremia and talk a little bit about vision loss and accessibility in general. Because, obviously a lot of the things and the challenges that you would have with Choroideremia could also be applied to other types of vision loss, partial blindness, and complete blindness.
And so, Chris, starting with you one of the things we've talked about before is that some of these assistive devices, low vision aids, aren't even necessarily covered by insurance and that there is not enough of these maybe technologies or solutions out there in the world. I was wondering if you could talk a little bit about what kind of things are really helpful and what are the gaps and what exists.
Chris: Lemme start by sort of. Reemphasizing the impact of severe vision loss and blindness. You know, the majority of people with who are, who are blind or with severe division loss are, are, are unemployed. The number's a little bit fuzzy, but it's definitely over half and we believe about 70%, only about 15% of people with severe vision loss or blindness get a college degree.
 About half of people that go to college don't, can't, make it through to complete their degree. Salaries and are, are lower for people with severe vision loss or, or blindness compared to non-disabled colleagues. So it really has a profound impact on people's lives. Not to mention the, you know, the, the social wellbeing, the mental health wellbeing of the individual.
It can be very challenging. You know, I, I consider myself in some ways a little lucky because I was able to, get through the educational part of my life and in my early career before my vision loss got severely severe. But even in my case, I quit practicing medicine about a decade ago to move into administrative healthcare where my work was being done on a computer.
And now, even in the last year and a half, ended up, ending my life in the workforce because I simply couldn't, you know, keep up with the pace of things and read to the speed that that needs to be done. So there's really, you know, a, a tremendous opportunity for the development of accessible software and other accessibility devices for patients with rare diseases.
I, I think I would start, as you say, with mobility and, you know, this day and age. When someone is diagnosed, they, they get told to wear a hat and sunglasses, and if their vision is worse, is bad enough, they give them a white cane. Well, it's kind of hard to believe that in our world, you know, you can lose a limb and have a prosthetic device.
I. Placed on it. Or you can have a heart attack and have these unbelievable stenting devices placed to save your life. But for a blind person, they essentially give you what defacto a, a, a tent pole with a tip and a handle on it. And they're, and that, and that's kind of what we have the ability to do, as you mentioned, as well, you know, the, these device, these accessibility devices aren't covered by insurance, oddly.
The, the white cane is considered by Medicare to be a self-help device, which is sort of strange because if you have a, a mobility challenge and you need a wheelchair or a walker, or perhaps a motorized scooter. Those things aren't considered self-help devices. They, they are considered to be mobility aids.
So I, I kind of question why that decision was made, because the can certainly helps me be mobile. But in its current day and age, those, those costs are out of pocket. There are some other devices that are available, but again they're at the cost of the consumer. And as we talked about, this is a group of individuals who generally are low wage earning and or,
on Social Security disability. So it can be difficult when you are presented with a device that may cost a thousand dollars or more. Do you have the funds to be able to support that or is it, does that need to be directed towards other things? So like I have a I have a, a reader and magnifier that I could, digital reader and magnifier that I can use.
For, you know, reading mail, reading books and other things like that, I, I was able to, to purchase it and use it, but it cost over a thousand dollars. So can the average, you know, can the average consumer do that with blindness? I think many of them can't. And so they're left using less ideal devices or, or maybe nothing at all.
There's opportunity for advancing the field, certainly smartphones, and , being able to walk around with a computer in your hand. There's tremendous opportunity for applications to be developed or for other technology to coordinate with the smartphone and, and assist with,
mobility reading and the like, you know, some of that technology, like screen readers and such, they exist, they're okay. Siri's fine. Anybody who's used Siri or similar assistance knows that it's not perfect and the transcription is not great. So you still have to be really careful when, when you're trying to use that.
But those things are helpful. We just need to move the needle further to make them more effective. And again, trying to make them less expensive so they're more affordable to the population. 
Dasha: Yeah. And, and Abby, I have a question in terms of specificity of partial vision loss versus complete, is there anything like when technologies get developed for blindness or partial blindness, do, do they need to be more specific to individual diseases?
Is different disease progression required? Different responses or different types of assistive technologies? Kind of looking at what you know. If someone is developing something, what should they be thinking about as they try to ensure that it encompasses the largest population possible, which might not be possible?
Abby: Yeah, absolutely. There are definitely different types of vision loss We've been talking about loss of peripheral vision. There are other diseases where patients primarily lose central vision. Like age-related macular degeneration would be one of the more common ones, but there, there are other more rare diseases that also lose primarily central vision.
And honestly, most low vision aids are more geared towards central vision loss. You know, all of the magnifiers. Which honestly, a lot of the aids are aimed at magnification. Both the digital ones and the, you know and, and others. Handheld magnifiers, wearable magnifiers. A lot of that is really more helpful with central vision loss.
There's really not much to help with peripheral vision loss, I mean, orientation, mobility training with a cane or with a leader dog. I mean, that's to help. With navigation, if you have peripheral vision loss or maybe complete blindness, both peripheral and central vision loss. But there's really not much out there to expand the visual field there.
You could do you can wear a reversed telescope, which makes everything smaller, but you have a bigger visual field. Everything's kind of minified the opposite of magnification or there you can wear like prism glasses to help bring. Part of the visual field that you don't see into your view. But other than that, there's not much.
So that's that's an area that could use improvement for sure. The magnifiers are good for people who still have some, some vision left and they just need things bigger for patients that are near complete vision loss, then more of the digital technology that can tell you what you're looking at,
you know, audio type technology is helpful. You know, wearable digital aids that could tell you what you're looking at. Essentially. 
Dasha: Are there any promising advances in things like haptic feedback or sort of technologies that are on the, on the verge of being developed that you, you see potential applications?
Abby: Well, you mentioned AI before. I mean, this is one area where, you know, even though it's not helping to, to translate treatments, it is helping, potentially with low vision technology. A lot of my low vision patients have gotten Meta AI glasses. And even though that's not technically a low vision aid, it's not developed or marketed as a low vision aid.
Patients with low vision are finding it useful to do, as I said, to tell them what they're looking at. The AI technology can identify the things in their, in their visual field and identify them for the patient. 
Chris: I was gonna just add that, you know, one of, one of the opportunities there and, and.
Advancing this research is to move from devices like the meta AI glasses or there's a device called OrCam, which generally uses sort of a static view of the world and then provides some description about it to then move to the next level of, of getting sort of live three-dimensional, video, a photograph of the world.
And that would help an individual be able to, to, to navigate, right? If you're, getting kind of continuous video of the surrounding world and getting feedback that could help somebody like me safely be able to get from, from one place to the next. But it doesn't, I know there's re there's work being done to design and develop these currently, but none exist yet. And I think the last thing I would touch on is, you know, the, the potential that the driverless vehicle could provide to the blind community. Obviously they're not they're not. Readily available to consumers yet. But. That's a huge impact towards an individual who you know, may not live in in an urban area and needs to get from, from point A to point B or get to go food shopping or what have you.
Current day and age, while things like Uber and Lyft are great, they, they, there is still some lack of independence and, and cost associated with that. A a driverless vehicle would truly, you know, change the lives of those with vision impairment. So we're eagerely awaiting those to arrive on the market, but not really clear when that'll be.
Dasha: Are there non-technological advances, just things that are happening in society or things like Uber, I imagine that have sort of made a difference where those who are entrepreneurially minded and innovative, maybe not even technologists, but they listening to this and they think, oh, you know, is there some way I could adapt what I do to, to this?
Could you give some examples of things like that, that either exist or could exist? 
Chris: Well, I think most of what we get through our, our smartphone is tremendously helpful to, to blind users. You know, as I, I keep going back to the well of mobility, mobility's, very much of a challenge and it's, you know, simple things that,
most people take for granted, like food shopping can be very difficult for a visually impaired person. So to be able to go on an application and not only choose your your groceries, but having delivered to you is tremendously beneficial. And now obviously those applications are, you know, ubiquitous for, for companies.
So that's one. Certainly ride sharing services like Uber and Lyft, and there's many others out there I know are. You know, very useful to get someone with a vision impairment from point A to point B safely and effectively. So I, I think tho those are definitely very helpful. I, I think I would say mobility and safety is a big priority for
people that can't be independently mobile on their own. So developing software that can improve that is really important. And then secondarily, bringing the outside world in for a blind user is, is really helpful. Whether it's, again, the access of goods and services, so, you know, social media those things can be, again, really transformative for patients.
Abby: You know, I think one of the issues that a lot of my patients run into is that there's not affordable, transportation for them, you know, and there's not support for them. So a lot of patients fall into a gap where they don't qualify for disability because they're not legally blind, but their vision's not good enough to drive.
There's kind of a big gap between driving vision and legal blindness. A lot of people think that, you have to be legally blind in order before you have to stop driving. And that's not true. There's a gap there. And so a lot of my patients fall into that gap and they need to keep working and they can't get to work and they can't afford to Uber to work every day.
And so, and there's no support for those patients, so that's really hard. 
Dasha: Yeah, and, and the mobility. I, I can see how it could affect all areas of your life. Obviously ability to earn an income, but to socialize, to get exercise and stay, stay healthy and, and mobile and active and, and feel, strong. What about psychological support?
What are some of the kind of challenges that happen when you're losing your vision and what kind of things have you seen in terms of mental health and support from that regard? I 
Chris: think most patients who need that support will get directed into. Sort of the same that, that you or anybody else would be of looking, you know, looking for a therapist, psychologist, psychiatrist, to be able to help with mental and emotional wellbeing.
There's a, there's a lack of those specialists, not surprisingly, who have a, who have an understanding of what it's like to live with blindness. So finding individuals who have that, that background and that history is, is difficult. And while it can be helpful to speak to anybody, and you know I've done so myself, having somebody that truly has a better understanding of what you're going through and the, and the, the challenges that you face every day can be really helpful,
not only for was the patient, but also for the clinician to sort of recommend coping strategies or recommend treatments that can be helpful for that particular patient. So there's, there's opportunity there. I mean, I certainly know mental health providers do a great job and they do what they can, but the more they can understand about the patient challenge, the better that they can be.
Abby: Yeah. And you know, I find a lot of my, it's true there aren't enough mental health providers that are familiar with low vision, but also there aren't enough mental health providers in general. And so a lot of my patients have a hard time finding somebody. And we can put in a social work referral, you know, our social workers,
can provide counseling and we actually, we have a, a, a research, a funded research program at our institution currently. 
Dasha: There's so much that we went over here and there's so many more things we could have dived into because every, every, piece of the topic from the genetic markers and genetic inheritance of disease to the specific progression and research and choroideremia to general low vision and vision loss assistive devices and technologies so much.
But I'm so glad we got to, to kind of at least speak at surface level about each of these topics. Chris and Abby, thank you so much for your time. Thank you so much. 
Chris: Thank you for having us. 
Dasha: Absolutely, and for our listeners, we know many of you are athletic and love to track and measure your health and fitness. If this describes you, then you should know about HYBRD spelled H-Y-B-R-D. Hybrid is the performance hub for modern athletes. They break down the silos between cardio, strength and wearable data to give you a complete view of your performance.
They are ex-WHOOP, ex-US national rowing team, triathletes / ultramarathoners, and are building the app they wish existed for their own training. This app, which just launched publicly on the iOS app store, was built by two UVA engineering alums. Links to download the app are in the description.
And if you love this episode, be sure to revisit episode 14 with Dr. Bethany Teachman to learn about free digital tools for mental health and stay tuned for an upcoming episode with Dr. Stan Crook about ultra rare, nano rare diseases later in this season. Please subscribe and share this episode to continue educating the world about rare diseases and choroideremia.
David: Thank you for listening to Biomedical Frontiers. Stories with innovators in healthcare. My name is David Chen and I'm the managing director of the Wallace H Coulter Center for Translational Research at the University of Virginia. Our mission is to help bring promising new biomedical research and technology into the hands of the provider and the patient.
If you found this episode valuable, please let us know by subscribing, following, or sharing, you can learn more about our promising translational research. Projects on our website. See links in the show notes.