Presenter: Ben Shaberman, VP Science Communications Foundations Fighting Blindness
Presentation on February 24, 2024, on Retinal Degenerative Diseases and Research
It’s an honor and a privilege to be here today to talk about retinal research and, some of the great work of the Foundation Fighting Blindness. And this is my third time at the Villages.
And I really love the community. It’s beautiful. People are so nice. Um, yesterday, after I got in, I decided to go for a run. I’m at the Brownwood Hotel. And I thought, well, I’ll go for a little run. Well, I got so lost. And I was interrupting golf cart traffic in a big way because I kept on stopping people and saying, Where’s the Brownwood Hotel and Spa? But everybody was really kind and helpful, and my run ended up being a little longer than I had planned, but I did find my way back home, so If one of you were one of the people I stopped, thank you for letting me interrupt your golf cart excursion. Anyway, I am going to talk primarily about research for retinal degenerative diseases.
And that’s what we’re all about at the Foundation Fighting Blindness. And those include conditions like age-related macular degeneration, and then there are a host of other conditions. What we call rare inherited retinal diseases, like retinas, but with me today are two of my colleagues who I liken us to the Three Stooges, and John, you can already tell he’s kind of like Mo, he’s always correcting and setting us straight.
Michael’s like Larry, and I think I’m more of the Curly type, as I mentioned upfront. But anyway, um, we’re happy to talk to you after this talk. As you walk into the exhibit hall, the first booth you will see, if you’re able to see, is the Foundation Fighting Blindness table. So please feel free to stop by if you have specific questions about what we do or some of the research I’m going to talk about today.
So just to give you a little background on the foundation before I talk about the retina and A& E and some cool research, is we’ve been around for more than 50 years. And we were founded by a small group of families back in the early 70s who were looking for answers to their retinal diseases. Back then, not only did we know little about the diseases, we really didn’t know a whole lot about the retina.
And these families got together and started raising money. And after a few decades of painstaking research, really in the early 2000s, therapies started moving into clinical trials and we even started to have some FDA approved therapies. One of the first therapies ever approved for the retina, really AMD, uh, in 2006 was, uh, treatment called Lucentis.
Is anybody familiar with Lucentis? Raise your hand or clap. That was really a game-changer in the AMD space. And I’m proud to say that the foundation funded some research that helped make Lucentis possible. We’ve come a long way since then for wet A& D, and I’ll be talking about that in a moment. But also A couple of years later, the first clinical trial for a gene therapy for the eye or any inherited condition was launched.
The treatment ultimately was FDA approved and it’s a treatment called Luxternum. Again, we helped fund that research. And it’s returned vision to children and young adults who are virtually blind. And these kids have a condition called labor congenital amaurosis. They’re born nearly blind. And after receiving this therapy, they were able to put away their canes. They could see the faces of their parents for the first time. Some could even see stars in the sky.
And those were the first Lucentis and Luxturna were really the first therapies to, uh, to get FDA approval. But since those early 2000s, we’ve had dozens and dozens of treatments move into clinical trials.
And now there’s somewhere in the neighborhood of 50 clinical trials underway for emerging retinal disease therapies. And the foundation is really focused. I’m advancing research to the point where we can move it into a clinical trial. And then we partner with biotechs and pharmaceutical companies to move treatments through clinical trials.
Now the foundation does a lot more. We have a no-cost genetic testing program. I don’t have a whole lot of time to talk about that, but if you’re interested In genetic testing come by our table. We can tell you more about how to access that. Okay. We have a patient registry to help people get on the radar screen of clinical trials.
There’s free genetic counseling that’s part of that. We have a lot of educational resources and do events like this all over the country. And in our 50-year history, we’ve raised more than $900 million for research. And right now we fund somewhere in the neighborhood of 90 projects around the world. Many in the U. S., um, also in Europe. And we need a lot of research for when we get more treatments.
So that’s my pitch on the foundation. But before I start talking about research and therapies, I want to make sure we all know what the retina is. It’s an amazing piece of tissue. It lines the back of our eyes. So the front of our eye is where the light goes through, you know, your cornea, your lens, through the pupil, through the lens.
It goes through the middle of the eye. until it finally hits the retina. And the best way to think of the retina, it’s like film in a camera. It captures light, and it converts it into electrical signals that are sent to the back of the brain. And then your brain takes that information to create the images that you see.
So the retina is very, very thin. It’s only half a millimeter in width. But it’s a powerhouse. It has more than 125 million rods and cones. Those are the cells that make vision possible by processing light. They absorb light and again convert it to that electrical information. But the rods and the cones are the cells that we’re often most interested in because they’re, they’re like the antenna of the retina to take in light and give you vision.
And what’s cool about the retina, and it, not only is it cool, it presents a challenge, it processes more oxygen for its size. than any part of the human body. More oxygen than the brain, heart, lungs so it’s a real workhorse and while light is obviously important for our retinas, for us to see, light can also be damaging so the retina needs to be really healthy, to protect us from all that light exposure. So, it’s important whether you have a retinal disease or not, to not smoke. Smoking is really bad for your retinas. It’s good to eat a healthy diet with a lot of fruits and vegetables. And it’s good to exercise and try to reduce stress. All of those things are important.
So, the leading cause of vision loss and blindness in people our age is age-related macular degeneration. More than 10 million people in the U. S. are affected by AMD, and I’m going to call it AMD from here on out. And the two biggest factors, well, I will say there are three. One, unfortunately, we can’t avoid.
That’s aging. The older you get, once you hit 55 or 60, the older you get, the greater your risk for AMD becomes. Smoking is a huge risk factor. And there are certain genes that, depending on how they’re configured, can increase your risk for AMD or even decrease your risk. So those are the big factors. And again, you can control that.
Uh, you can control, um, some of those by your lifestyle. And it’s really important to see a doctor on an annual basis even if you don’t have AMD, to see how healthy your retinas are. And you can usually see a doctor. See if an MD is developing and the earlier you address it, the better chance you have to save your vision.
So I strongly encourage everyone to get an annual eye exam. Again, whether you have an MD or not, not only to check for an MD, but to see if you have things like glaucoma. Or maybe a corneal issue, whatever. There are conditions of the retina, of the eye, that you don’t necessarily notice. But if you can see the train coming through a good eye exam, you can address those situations and have a better shot at preserving your vision.
So, age-related macular degeneration, starts off with the accumulation of these deposits underneath your retina. And I think the easiest way to think of those deposits, is they’re somewhat similar to the deposits that we get In our vascular system, atherosclerosis, as we get older, some people have more, some people have less.
But as those deposits accumulate, they can lead to AMD. Most of us have the deposits. They’re called drusen. The question is, do you have enough of the harmful deposits? where you might lose vision and develop AMD. Now, everybody who gets AMD starts off with what we call the dry form. And the dry form is just those deposits reaching a certain point where you’re at risk for vision loss.
And then once you develop these Early dry AMD, really three, four things can happen. One, you may never have vision loss. There are a lot of people with early dry AMD where it doesn’t progress to the point where it causes a problem. The second thing that can happen is the dry AMD can get bad enough that it starts causing some cell loss and a condition we call geographic atrophy.
That’s advanced dry AMD. The third thing that can happen, and it’s not mutually exclusive with dry AMD, is the development of leaky blood vessels underneath the retina. which is known as wet AMD. So you can have geographic atrophy and wet AMD at the same time. So there are different paths that AMD can take.
And I’m just curious by a show of hands, how many people have at least early age-related macular degeneration? If you don’t mind disclosing the results. That’s a pretty significant number. And again. It’s a, it’s the leading cause of vision loss in our, in our demographic. So excitingly, there are several treatment options for wet AMD that have been approved by the Food and Drug Administration.
I mentioned the first one, Lucentis, that was approved in 2006. Since Lucentis has hit the scene, there have been a few others that have been approved. And the benefits of these other treatments, like Vobizmo and Ilea, are that you need fewer injections. Instead of getting a monthly injection with a high dose Ilea or Vobizmo, you can get a monthly injection with Ilea or Vobizmo.
In some cases, the injections can be as infrequent as every four months. Does that mean if you’re getting Lucentis right now, and it’s working for you, and maybe you’re getting it every other month or every few months, and you’re doing well, you should change? No. That’s not necessarily the case. Really, you talk to your doctor and together with your doctor you make a decision about what’s best for your wet, age-related macular degeneration.
There are just newer and better options that may be better for some people. So a lot of good options with wet AMD. The key to staving off wet AMD is being vigilant about the injections and getting them when you first notice vision changes. So you take your, your I. V. s, get into an eye doctor, and they can diagnose what AMD, and you can address it.
Now, dry AMD, the advanced form, has been a tougher nut to crack. But excitingly, over the past year, we’ve had two FDA approved therapies for dry AMD, the advanced form, again, we call Geographic Atrophy or, for short, GA. Those two treatments are called Cyfovirin and Izervit. And those were, again, were approved last year.
And the idea behind those treatments, or the goal, is to slow down the progression of, of deterioration of the retina in people with dry AMD. And the bottom line is, if you have geographic atrophy, or you’re getting close to having it, talk to your doctor and see what he or she says about getting these treatments to stay involved.
and slow the advancement of cell loss for dry A& D. Not all retinal doctors at this point are prescribing the dry A& D drugs. Some are, some aren’t. They’re still kind of new and I think that the more conservative retinal doctors are waiting to see how it performs. But it’s a good option. Um, if you, if your doctor thinks it’s right for you.
So talk to your doctor and, and together again you can decide what you think might be best. So now for advanced AMD, there are newer therapies that are still in clinical trials to replace some of the lost cells in the retina. Namely, a layer of cells called RPE cells that provide really important support for your rods and cones.
Those are all still in clinical trials. We’re learning from those trials and hopefully in the next few years, something will cross the finish line. There’s also, um, an approach called optogenetics, which is moving into clinical trials as well. Now, optogenetics is a really cool way of restoring vision for people who have really advanced vision loss.
So if you’re down to maybe only seeing hand motion or worse, you see nothing or just a little light perception, optogenetics may be relevant to you. Again, it’s still in clinical trials, it’s not widely available, but it is being evaluated in humans. And the way optogenetics works is if you’ve lost a lot of your rods and cones, those really critical cells for vision, there are other cells in the retina that survive after the rods and cones are gone.
Those are called bipolar cells and ganglion cells. And some really clever researchers were able to deliver either a gene or a chemical that to those surviving cells to make them light-sensitive to work like a backup system for rods and codes. Those cells aren’t normally light-sensitive. And in a few different clinical trials, patients who have received that light-sensitive therapy have had some rudimentary vision improvement.
They can see shapes. They can see, um, people in front of them, or movement. Um, one gentleman was able to see his dog running through the snow. The snow provided some good contrast. And they’re able to just navigate better. And we don’t expect, at least at this juncture, for optogenetics to give people, like, high-resolution vision.
But if you’re down to nothing, or very little, it’s really showing a lot of promise to provide some rudimentary vision for people to have some independence. And so, optogenetics, very exciting, with four or five clinical trials underway. And you can stay tuned to that approach by visiting our website, fightingblindness. org. Yours truly writes articles about the latest developments in a lot of retinal research. But I’m, I’m pretty excited about the opportunity optogenetics has for restoring vision for people with advanced vision loss. So that’s kind of what’s going on for age-related macular degeneration. And I want to touch on one topic.
There’s one other emerging approach that I think is pretty exciting, still at a relatively early stage, and that’s gene therapy. for both dry atrial macular degeneration and wet AMD. So, in both conditions, I’ve already indicated that you need regular injections of these therapies in your eyes to keep the disease from progressing, or at least slow it down.
Well, imagine if you were to If you can get one injection underneath your retina that would work for many years or maybe the rest of your life to keep either wet or dry AMD at bay. That approach is called gene therapy and what they do is they engineer a virus to deliver a gene to your retina that makes the same treatment that you would be getting through the regular injection.
So basically, it’s like putting a little drug factory in your retina to continually make the treatment to prevent the wet and dry AMD. So there are a few clinical trials underway for that. Wet, for wet AMD, it’s a little further along and we’re seeing some encouraging results. And I would estimate, please don’t pull me to this, that in another two to three years we could see gene therapy for wet AMD cross the finish line and get FDA approval.
For dry AMD, we still have a little further to go, but it’s very exciting and obviously it would be great if people didn’t have to go to their eye doctors on a regular basis to, get these treatments.
So let’s, um, let’s talk about gene therapy as it’s being used for inherited retinal diseases. So I’m gonna, um, stop talking about AMD and move over to the inherited retinal diseases like retinitis pigmentosa, Stargardt disease, and so on. So these conditions are all caused by a single mutated gene. It’s a gene that’s doing bad things in the retina.
And the mutated gene for each person, there’s again, one gene that’s the culprit. It could be one of many, many genes, but if you can identify which gene, if you have, let’s say retinitis pigmentosa if you can identify what gene that is, there may be a gene therapy to replace that bad gene. And right now we have clinical trials for a number of genes, RPGR, um, RS1, G0I2D, and I realize that may sound like gobbledygook to everybody, but it’s important if you have a rare inherited retinal disease, it’s important for you to know your gene to see if there is an emerging gene therapy.
And I talked about, look, sternum earlier. As the first FDA approved gene therapy, and that works so well, it really provided a lot of momentum for gene therapy development. And so we’re seeing a lot of activity in this space. And like the therapies I was just talking about for wet AMD and dry AMD, those gene therapies, the ones for the inherited retinal diseases, you probably only need to use one injection.
And again, we’re engineering viruses to be safe and to deliver the therapeutic gene to the retina. It’s really, really cool stuff. Now, another approach to saving vision in the retina is to prevent or mitigate oxidative stress. So your cell’s oxidators are constantly processing oxygen, but when you have a disease or stressors, you have something called oxidative stress, and that can make things a lot worse.
And so, researchers are coming up with new ways to what we call mitigate oxidative stress. And there’s a drug called N acetylcysteine that has been approved by the FDA. It was developed many years ago to treat a lot of different conditions. Researchers at Johns Hopkins studied it in animal models of retinal disease, including AMD, RP, and other conditions.
And they saw that it did a really nice job of slowing vision loss. So they moved it into a clinical trial for humans. And that clinical trial is ongoing. Underway across the country, even in Europe. Right now, they’re just studying it in people with retinitis pigmentosa. Now, we helped launch a company to make that drug even more powerful.
And we call that drug NACA. So they added what’s called an amide to it to make it even more potent. And we helped launch a study. Australia for people with a condition called Usher syndrome. That’s another level condition, and we’re waiting to hear results on that. But these are both oral medications that you can even buy over the counter.
Um, NACA is still under development, but a great way, regardless of the gene, even independent of your disease, you might be able to slow, And there are many other approaches like that that are either in clinical trials or moving toward clinical trials. We love these gene agnostic therapies because they have the potential to help so many people.
So, I also want to touch a bit upon, upon, uh, Cell therapies for both AMD and inherited retinal diseases. So the idea behind most cell therapies is you’re going to replace the cells that have been lost to disease. And sometimes you’re replacing rods and cones, sometimes other cells in the retina. And what’s really cool, it’s an approach that we’ve been funding now for many years, and it’s just starting to move into human studies, is a way to derive retinal cells from your own blood or skin.
And the way researchers do that is they take a small sample of blood or skin, and they genetically tweak those cells. to revert to a stem cell like state. So it’s like turning the clock back on these cells, so they become stem cells. And then you can coax those cells forward to become the cells that you need.
Really, any cell type in the body. In our case, we want to make them inter-rutinous cells, rods and cones, or RPE cells. And that is now being done. And actually, In a clinical trial at the National Eye Institute in Bethesda, Maryland, they are doing, they are using that approach for a geographic atrophy treatment for advanced dry AV.
It’s very early, we’re still learning, they haven’t reported efficacy yet, but this approach has moved into humans. They’re doing it for retinitis pigmentosa back in, or over in Japan. So it’s a really, really cool approach. Cell therapies aren’t quite as far along as the gene therapies, but we’re trying to get some momentum there.
One thing I want to caution you on, especially if you’re all Floridians, there are clinics in Florida and other parts of the U. S. and overseas that will tell you they have a cell therapy that if you pay for it, it will restore your vision. And these are bogus clinics. Right now, for the eye or the, well, I should say for the retina, there are no FDA approved cell therapies.
So if somebody’s trying to sell you a therapy, a therapy you have to pay for, but they’re claiming it’s going to restore your vision, do not take it. If you have any questions, you can reach out to us about it. But I know for a lot of people, You’re really anxious to find some solution, and they sound really good, but do not embark on a cell-based therapy that you are being asked to pay for.
I think more of those clinics are in South Florida than here in Central Florida, but there may be clinics up here. So, cell therapies, there’s a lot more I could talk about, but due to limited time, I’m going to talk about one more approach to treating blindness that I think is exciting. And this is something that’s still many years away from becoming, uh, um, becoming a reality.
And that’s a whole eye transplant. Now, if you would have asked me about whole eye transplant a few years ago, I would have said Don’t think about it. It’s so far off in the future. It’s such a challenging effort. Um, it’s just not really on our radar screen yet. But earlier, I guess it was in 2023, when researchers performed the first whole eye transplant.
And they had some encouraging success. So the person who got it, to my knowledge, has not had restored vision, but they were able to successfully get the eye in the eye socket and get it to survive. And get it to not be rejected. And that’s a huge step. Because getting an eye transplanted into another person there’s so many things you have to do for it to even survive and work.
You have to get the blood vessels connected, the muscles, the optic nerve, if there’s any hope of vision restoration. And you want to make sure the eye isn’t rejected by people. The recipient’s immune system. Many, many, um, variables that you have to consider when doing that. But that first transplant was a huge step forward.
And now we’re part of a government program. We’re helping, um, get off the ground to improve and move whole eye transplant forward. So someday, that may be an answer for somebody who has That’s a really serious eye condition, and maybe their optic nerve is gone, or they’ve lost an eye, or they’ve lost an eye, let’s say, in combat, or to whatever, that whole eye transplant could be a reality.
So, Ed, I think, I think I’m at a good point here. Yeah, I think we have time for a few questions. Okay. All right? And I’m going to give this mic to Michael.
And thank you. I know I just rattle on. But again, we’re over, the first group is you walk in, Foundation Fighting Blindness, we’re happy to chat with you about, mostly retina, because that’s where we’ve been.
Um, Michael, I see you’re coming here, I’ll just hand you the microphone. Have they developed anything for people whose retina has never fully developed?
Uh, that’s, that’s a great question. Um, so a whole eye transplant might be an option someday, but right now it’s, the focus is on cell replacement and what I would say is it depends how much retina you do or don’t have.
And you may need like a whole retinal transplant and that’s honestly something that’s not quite Um, ready to be studied in the future. So, I know that’s not the most encouraging answer, but there is work toward it. It, it depends on your particular case and how much revenue you do have for the person. Um,
I do have vision, so I must have cell, okay, well then maybe some cell replacement.
Depending on what cells you have or don’t have. Maybe that is an option and that is moving into clinical trials. We can talk more about that. You know, that’s a great question. And I would give a similar answer to the woman who just asked about under development of the retina. It really depends where the scarring is. And what cells might need. To be replaced, but depending on where you’re at visually, something like optogenetics might be an option to harness other cells in the retina for vision. Um, it, really depends on where the scarring is. So I’m happy to talk more about that if, if, if you want. Um, later on. Few questions.
Hi, uh, you talk about gene therapy. Uh, would that help somebody with, uh, Neuropathy, Optic Neuropathy?
Um, it depends on your form of Optic Neuropathy. And let me explain what Optic Neuropathy is. Your retina is connected to your brain through what’s called the optic nerve.
And people with optic neuropathy, they have some issues with their optic nerve. So if your issue has a genetic cause, then gene therapy might be relevant. So it depends. It could be. And there are some optic neuropathies www. ottobock. com For which gene therapies are being developed, if again, there’s a genetic cause.
You guys are really coming up with the tough questions. That’s good. This is probably something that we should have understood before. If you’re getting injections in one eye for wet over a period of time, does that ever then become dry?
Um, so the dry and the wet are really two different things that are happening in the retina. And they can both happen at the same time. So you could be getting injections for wet, let’s say, I’m just going to say your left eye, and you could develop The two things can happen simultaneously, not necessarily because you have wet, but just because the dry is progressing. But with the therapies that are out there now, it’s depending on how severe each condition is, you can get treatments, both a dry AMD and a wet AMD treatment in that hospital.
This doesn’t sound like a party, but you know, it is something that you can do.
Two kinds available for that generation. Is there one that is preferable?
The short answer is no. Um, they both work about the same. They in clinical trials, they slow the disease by about 25% and they work similarly. But I would talk to your doctor because your Doctor may have a preference. for some reason, and they’re the people on the front lines that are actually injecting them and have experience. And so I would talk to your doctor, but efficacy clinical trials, they’re similar.
Um, I think I’d like to… Good. Sure. Um, so people could move into the exhibit hall.
The foundation will be at their table, but I’d like to thank you for the presentation. And we need to look at what’s in the exhibit hall, right?
