Gene Therapy for Retinal Disease

welcome to red and health for life from the president's corner brought to you by the american society of redness specialists i'm your host dr tim murray coming to you from miami on each episode we'll bring you inspiring conversations about your site and the special role the retina plays in making healthy vision possible we'll hear from expert reading specialists as well as directly from patients about living life to the fullest with retinal disease join us and learn how to safeguard your retina health for life welcome to the american society of retina specialists retina health for life from the president's corner on this episode we're going to talk about gene therapy which is leading to breakthroughs in saving and restoring vision for people with retinal disease today i'm happy to welcome my colleague and fellow redness specialist dr thomas chula of the midwest eye institute to discuss this exciting scientific advancement dr chula is a world's authority on gene therapy applied to the eye and it's truly a pleasure to have him join us welcome tom thanks for having me tim pleasure to be here really a pleasure so um tom this these uh videos are really focused to reach out toward our patients and and our families and i think one of the excitements in our field and what has been driving a lot of our research interest has been gene therapy i continue to get asked about when will gene therapy be available for me virtually every clinic day so i'm curious if you have that experience in your clinical practice and then could you take us into really what drove you to an interest in gene therapy and then take us again into what gene therapy really is for our patients well sure absolutely so patients are i'm very excited about all that's happening in retina retina is an incredibly interesting field with all sorts of innovations with therapies like gene therapies with diagnostic tests and even with um surgical innovation where we can help patients so much better now than than we could back when you and i were residents tim i i got interested in in retina and research when i was doing my residency at mass eye and ears in the 1990s and i was exposed to her absolutely brilliant group of young faculty members who are working on angiogenesis under the legendary judah folkman and they did the entire ecosystem was really a special place because he had all these innovative hard-working faculty who ultimately helped develop anti-veg therapy that we all use in our practice every day and you know oftentimes we can restore sight in patients with macular degeneration and diabetic retinopathy this really inspired me to pursue clinical research in retina later on when i joined the faculty at indiana university uh it was also a really exciting time it's the only medical school in the state and the largest medical school in the country with 11 campuses back then we had an angiogenesis lab and we started clinical trials working on early trials of anti-vegf and what what still sticks in my mind now 20 years more than 20 years later is that i vividly recall how we had patients uh in these trials and and i always thought we were just going to help slow down their vision loss and i i realized what a remarkable innovation that we had stumbled upon um when patients started coming back to my clinic with better vision so it's a really exciting heady time and this really um inspired me to continue with with retina and retina clinical research and and i got essentially just hooked on on this exciting innovation um and so i think you know since then we've come a long way and you know now we're talking about um gene therapy um and so i think i think you asked me about uh gene therapy and and what it is and you know basically it's this rapid evolving technique and it essentially manipulates the genes in patients to to treat underlying disease typically genetic materials introduced into the cell and that restores production of a protein that may otherwise be faulty due to a patient's dna yeah i think that's really fascinating and and i think that you know you've had two really great opportunities to partake in therapies that are literally game changers and i agree with you i think when you start in a lab like you did at mass pioneer and like i did when i was at johns hopkins i think it really just generates that kind of interest to continue to explore some of our colleagues explore by staying in laboratory fields but some of our colleagues want to translate that research and and i see you as an excellent example of that so you're taking research from the laboratory and really moving that into clinical care and for me that's the gold standard i'm always excited about that so in in gene therapy it sounds so simple that you first find the defective gene and you just replace it but i think that you and i both realize the devil's in the details so ophthalmology really has been a leader in in sort of many areas in medicine but i think that you and i both would agree that the first gene therapy to be effective and fda approved is for the eye so could you tell us a little bit about what that disease is and what that therapy is and how do we treat the the involved patients the disease is libre congenital amaurosis and it's a really rare absolutely visually devastating disease it's caused by a variety of gene mutations in in the rpe 65 gene and that that's a gene that produces a protein which plays a key role in our visual cycle it's partially responsible for vision uh classically libra's congenital amaurosis presents an infants and children with loss of night vision loss of peripheral vision and ultimately these children lose their central vision gene therapy essentially has allowed us to add a normal rpe 65 gene that restores the visual cycle in these patients um in in and it's it's really a essentially a very life-altering therapy for these patients and their families during the approval process i got to go to the fda and hear patients and their families give testimony of how they could see their parents faces for the first time they could see stars in the sky for the first time they could go trick-or-treating for the first time or even see snow for the first time but i i i think you mentioned i'm adding a gene to cells that are affected and that's essentially what we're doing with this first gene therapy and i just wanted to back up a bit and just explain that as you mentioned the devil's in the details so gene therapy can be one of many forms what we're talking about is something called gene augmentation again adding a gene to a cell to replace a missing or defective gene but there's other types of gene therapy in the news another type for example is gene editing when we revise the existing genetic code in a patient's cells and there's also gene inactivation when we silence a faulty gene so basically libra congenital amaurosis with with the first therapy luxterna is a form of gene augmentation therapy so that's fascinating but as you've said because labor's is so rare we touch a very small part of the population that has this disease it's a it's an incredible advance for that disease and for those patients which is interesting but we're also very aggressively as as you've been involved looking for other therapies and i get approached about a very common disease day in and day out in my clinic which is age-related macular degeneration there's been some excitement about the possibility of a gene therapy for age-related macular degeneration can you take us through that a little bit what are your thoughts and where do we stand great question really interesting concept so so we started this conversation tonight with talking about anti-vegf therapies for diseases like wet macular degeneration and diabetic retinopathy these are some of the the most prevalent causes of irreversible blindness or central blindness in the industrialized world and as you know we can we can inject therapies in patients eyes unfortunately they often have to come back almost monthly and sometimes indefinitely for that treatment so interestingly gene therapy can be used to have the retina produce its own therapy in what we call a biofactory approach so for example instead of administering monthly injections of these anti-vegf therapies to patients with macular degeneration or diabetic retinopathy a one-time gene therapy could theoretically lead to lifelong production of medication within the eye and basically free patients from that treatment burden of monthly injections so that that's a very exciting concept and it also shows the versatility of gene therapy we we mentioned uh treating lieber congenital amaurosis a very rare in fact ultra rare disorder with the first approved therapy luxterna and on the other end of the spectrum use gene therapy as a bio factor to treat very common disorders so it's a it's a very versatile modality and i think the entire retina community is equally looking forward to ultimately using this on patients it could benefit patients and their families in so many ways it's interesting too because labor strikes at you know at birth and macular degeneration strikes often in our seventh eighth and ninth decade so this the the same concept of gene therapy targeting both spectrums of life for our patients i think my patients are very excited about the concept of a bio factory and they can understand that really intuitively that their eye could be placed in a position to make something that helps and what's fascinating i think and you do also i believe is that this can be a treatment for multiple diseases that pivot around um alterations in vegf so that's kind of super exciting so maybe it'll work in amd maybe it'll work even better in in in diabetes any thoughts on that we often treat patients now who have swelling in their macula from diabetic macular edema but what's really interesting is to be able to treat patients with a biofactory therapy that produces an anti-vegf these would be patients who have diabetic retinopathy but not diabetic maculoedema yet or not proliferative diabetic retinopathy yet so we could potentially treat patients with early stages of diabetic retinopathy and that would actually prevent them from even having the disease in the first place or progression of the disease in the first place so so it ultimately could it could be a almost a comprehensive strategy to prevent uh complications of diabetes and diabetic retinopathy with respect to proliferative retinopathy or diabetic macular edema so i think that that's very exciting as well it actually could alter the course of disease for patients yeah i think that's i think it's fascinating to go from one specific gene defect that treats one very specific disease to a concept that will enable us maybe to treat patients with multiple stages of multiple diseases so that's that's incredibly exciting tom when when you've looked at this the first therapeutic strategy with luxterno requires a surgical placement of the drug underneath the retina which has been technically challenging in some instances can you take our patients through in their families what are different approaches to to get gene therapy effectively into the eye and where are you thinking we would like to go as a best case approach great question um so so obviously we we want the gene therapy to uh essentially treat the correct layer of the retina currently we do surgery where we perform a vitrectomy we inject the gene therapy under the retina in order to expose the photoreceptors or rods and cones and the pigment cells that support the rise in cones to the gene therapy that is a a surgical procedure in the operating room it does have some risk um but but ultimately you know when we're treating patients with diabetes or elderly patients with macular degeneration it would be best for the patient to be able to do this in an office setting so another strategy is to treat with an intravitreal injection there's at least one company looking at that in a clinical trial and another strategy is to uh treat in the office with the supercorridal injection and there's another company uh uh assessing that in the clinical trial currently so basically we have the the sort of a standard surgical procedure in the operating room and then we have two office-based procedures that are currently in clinical trial yeah so for from a retina specialist perspective many of us are very comfortable in the operating room underneath the retina or on the retinal surface but virtually every retina specialist is comfortable with an intravitreal injection and that's how we treat the majority of our patients with complex diabetes and complex advanced stage related macular degeneration so i can easily see how transitioning to an injection in the office that would have a sustained effect would literally fundamentally change the management of our patients i think i think that would be in some ways what we would all be hoping for the suprachoroidal delivery a little bit more complex but is a very doable procedure in the office also but i keep pushing toward that interventral injection so that's that's where my hopes will lie for my patients angry it's very exciting and you know i think there's there's um multiple shots on goal here so so hopefully you know over the next few years we'll have an entirely new spectrum of very uh beneficial patients for treatment so one of the issues with with gene therapy that has come up with the luxderna approach is when are patients best benefited by surgery so are you thinking that there are going to be some changes in the way we approach our patients either at the age of treatment or do you think maybe patients will benefit from a wider application of the gene therapy delivery are there any thoughts about how we look at that are patients is some age too young tongue for patients to have gene therapy probably yes we know that the eye isn't fully grown until about age two or so they're still cells undergoing maturation in the eye so so we want to have the eye you know essentially be fully grown with with with anatomic landmarks that are more readily familiar to retinal specialists even pediatric retina specialists the surgery may have more risks in younger patients on the other hand if you wait too long there's a risk of amblyopia where if vision isn't stored in a child earlier in life uh their their their brain never really learns to see so to speak so it's probably around age three to four it may be the best time to start considering uh this therapy for lux stern on the clinical trials that was the um the lower limit of age in those patients so i think that's probably where we'll start but obviously we have a lot to learn and going forward things will evolve as they have in retina so i think that's fascinating one of the things that i think that happens when you develop first treatments is that we're able to apply some advanced imaging technology now to to our patients even at very young ages and i think in in the past sometimes we would see these children and and it would be we would we would observe them but we wouldn't really be focused on providing ongoing evaluation i think the game changer for this has been the ability to do gene testing on children young children especially that may have alterations that are previously unrecognized so could you comment about if if i'm uh if i'm a dad and my my young son has this very rare diagnosis is there a benefit for me to ask that there be a genetic screening test done and how do we do that you may have a great point um the the field has evolved with respect to diagnosis and in a tremendous way um you know classically clinicians would um examine the patient very uh carefully and uh they'd be also pattern recognition process in the clinician's mind and then as retina has evolved with diagnostic technology we became better at applying office-based diagnostic technology like imaging like oct imaging and angiography and now we're moving into an era of genetic diagnosis so it's the ultimate personalized medicine so absolutely if a patient has a retinal disorder at a young age it would be potentially very beneficial to undergo genetic testing that would allow a a molecular definitive diagnosis which in turn would allow for appropriate counseling appropriate understanding of the prognosis going forward and ultimately allow a patient to be screened perhaps for clinical trial be it with gene therapy or other therapies currently undergoing assessment and even if if a molecular diagnosis is established and there is no current clinical trial there are multiple clinical trials planned some of which are gene-specific and there are some non-gene-specific gene therapies that are being developed and maybe in clinical trials soon so i think the point of of having your child evaluated on a on a molecular level for for the gene therapy potentials is critical and that's that's kind of new for us um and and i think that that's really important for our our patients and and their families to know that that option is available i also think that there are specialty centers that have more experience potentially in both the evaluation and treatment of patients there's been some discussion about whether um children in particular benefit from being managed in a specialty center do you have any thoughts on on is is that type of unique gene therapy that requires a complex surgical approach should we think of that maybe in specific centers where something that may be much more traditionally available to other retina specialists like intravitreal injection or supracorrodal placement may broaden the the access for patients you know exactly um you know anytime there's a disruptive innovation uh in health care um oftentimes uh these these these disruptively innovative therapies are offered in in large hospital systems that have the the capital to buy all the equipment and the specialized training and then um over time these disruptive innovations um slowly become in a way commoditized where where the the technology becomes less expensive uh where the training becomes uh more widespread uh particularly in this age an era of the internet uh information is disseminated so quickly so i think initially with the with a with a very new therapy it's very common for it only to be authorized only for it to be offered in specialized centers but over time uh the the the therapies um as i mentioned they become almost commoditized to the point where uh more and more clinicians in practice um have it in big cities initially and smaller and smaller cities and ultimately the technology gets widely disseminated and that enhances access for patients so i think this is a good thing and i think ultimately you know sub-retinal surgery gene therapy will disseminate to more local providers and then as you and i were discussing once we have office based administration procedures it will become even better with more widespread access yeah i think that's i think that's exciting so you know like everything else first there's maybe limited access as we've said but then it broadly disseminates us it becomes more approachable outside of an academic center or a specialty center absolutely i tell my patients that you know that i'm comfortable talking to them about existing and potentially future gene therapies but not every retina specialist may be so where should we push our patients to look for additional information that's a little bit more appropriate than some of the general google sites that get looked at for gene therapy well the best source of information of course is the american society retina specialist podcast hosted by tim murray but of course the american society retina specialist has a lot of information on the website for patients as does the american academy of ophthalmology and of course the foundation fighting blindness has been very involved with inherited retinal disease and gene therapies most importantly patients should um uh seek advice from their own primary um retina specialist who um has access to these sources and beyond so i think especially for for parents that have a young infant that has a complex diagnosis i really think that's the opportunity to make sure you're seeing somebody that has specialty experience either a pediatric retina specialist or a pediatric ophthalmologist that has specialized in inherited retinal disorders because to me that's such a pivot point early to better understand what may happen for your child and what the options are for for you at a time when options are changing very quickly and i also like the national eye institute for the national institute of health as as a resource for patients they are very focused on how they present information and it's been very well evaluated as it is for the american society of redness specialists so so tom being being the person that's really actively involved what are you most excited for in gene therapy over that next maybe two year horizon well i think as i mentioned um some of these biofactory approaches uh could have just an enormous impact on our entire field an enormous impact on patients and their families having a gene therapy that sets up a biofactory in a patient's own eye to produce its own therapy could really change the course of disease for patients uh it could change essentially how we practice and it could have a huge impact on on society on the ability for senior citizens of macular degeneration to live independent lives uh for a longer time period for diabetic retinopathy patients to avoid some of the complications of diabetic retinopathy we discussed and even if these therapies um uh aren't necessarily uh one and done therapies you know even if even if they don't work as well as we hope if they even just decrease the treatment burden that would be a huge benefit to patients and their families and society so it's a very exciting time for for retina and i think as you mentioned earlier you know you and i have been very privileged to be in a field that has seen so much disruptive innovation you know we i started my career and i think you started your career on the same time where we we saw anti-jeff therapies come of age and now to think you know in a two-decade span to see uh gene therapy come of age and retina and and really it's very exciting to think that the very first gene therapy for genetic disorder in all of medicine happened in retina and it's really just amazing uh to witness that so i think we're on the cusp of of another huge paradigm change and it's just going to have tremendous uh impact on society um and i think it will benefit patients greatly i agree with you i think this is going to be an exciting you know next couple of years and i do think that it has the potential to shift how we manage virtually all of our patients in a red and specialty practice so that's incredibly exciting and i also think as much as it speaks to the good research and and relationships that we've had we also are blessed in retina of having very brave patients and very brave parents and family members who are willing to let us treat their children with novel therapies that that are not yet understood it really is an interesting concept to think about something going from a laboratory into animal research and then being able to treat the first patients with that i think it's all of all of what you and i both went into to medicine for so tom i'd like to thank you for joining us at our asrs retina health for life podcast thanks for tuning in to redding health for life from the president's corner you can watch and listen to more episodes on the asrs youtube channel and on popular podcast directories including apple podcast google podcast and spotify for even more information about safeguarding your vision for a lifetime visit asrs.org patients and follow asrs on both facebook and twitter retina health for life is made possible in part through generous support from the foundation of the american society of retinal specialists allergan genentech novartis and regeneron pharmaceuticals see you soon

Channel: American Society of Retina Specialists

Views: 2,961

Rating: 4.9487181 out of 5

Keywords: gene therapy, retina, retina specialist, ophthalmology, healthy vision

Id: JAIdAYNZ44k

Length: 28min 19sec (1699 seconds)

Published: Thu Jan 28 2021