As someone with a visual impairment, getting around once felt overwhelming. I was plagued by the “what ifs.” What if I got lost? What if I missed a bus or got off at the wrong stop? What if I couldn’t find the right platform at the train station? If you or a loved one is dealing with these concerns, this article is for you.
The good news is that over time, navigating has become easy for me. Because of my experiences, I’d like to share some tips for moving through the world with a visual impairment.
Step 1: Orientation & Mobility
It is important to learn how to use a cane and practice using it every day. Many people with vision loss live in denial of their visual impairment. If you’re not currently using a cane or a guide dog and have recently bumped into something you didn’t see, start using one.
Once you’ve mastered the basics of the cane, learn to navigate independently in your immediate neighborhood. (Parents, this is when you need to step back.) Have a friend or family member walk beside you the first time, pointing out obstacles and naming streets as you cross them. When starting out, it can be helpful to count how many streets you cross before you need to turn. Consider making notes on your phone to help you remember. For example, “To get to the doctor’s office, turn right out of my house, turn left at the first intersection, turn left after walking under the train bridge, and cross two streets before turning right. The doctor’s office is the first building on the left.”
If you are nervous the first time you try the route alone, have someone walk behind you and ask them not to talk to you unless you get completely lost. It is okay to get a bit lost! Part of becoming a better navigator is making mistakes. You can also video call a friend or family member if you need help.
Step 2: Generalization
Eventually, you will start to notice patterns such as how buildings are spaced, that street addresses with odd numbers are usually on the east or south sides of the street, and the typical layout of train stations, etc.
At this point, you won’t need someone’s help traveling a route for the first time. Instead, you will use the tools available to you—reviewing routes before you leave your home, leveraging GPS along the way, and not being afraid to ask someone to confirm your location or that you are at the correct building.
Step 3: Challenge Yourself
When I was in my second year of university, I was invited to attend an event to receive a scholarship I’d won. But it was two hours away. I called my mom to ask for a ride. She lived an hour from me in the opposite direction from the event. She said that if I wanted to go, I’d need to figure out how to use the bus on my own. It was one of her best parenting decisions.
I was terrified and had to ask a lot of people for help along the way, but I did it. It was an eye-opening experience and set the wheels in motion for me to feel comfortable traveling. In previous articles, I’ve talked about hiking in the mountains and trekking up Mount Kilimanjaro. These amazing experiences wouldn’t have been possible without a lot of experience negotiating daily life with my visual impairment. With enough practice, I am confident that you can reach a point where you can travel as easily as I do.
Growing up means encountering everything for the first time. Adolescents and young adults move through life much like advancing through different levels in a video game; each new setting and challenge offers opportunities to learn and master additional skills. In life, as in video games, abilities are not infinite, but progress is possible. Ashley Hunter, a young adult living with Leber congenital amaurosis (LCA), has always found refuge in video games and knows firsthand the connection between playing them and facing life’s challenges.
Ashley posed with her cane
Life Level One: Diagnosis
Early in life, Ashley’s symptoms were misdiagnosed as neuroblastoma. When her doctors observed nystagmus (roving eye movements), they then thought she might have a cancerous brain tumor. Finding out what was wrong was her first major life challenge. After three years of extensive testing, doctors determined that she didn’t have a tumor but instead had LCA.
Years later, when she was about 27, genetic testing revealed that Ashley had LCA caused by a mutation in the CRX gene, also known as LCA7.This form of LCA is often severe and has an early onset, resulting in significant visual impairment from infancy. It is usually inherited as an autosomal dominant trait, rather than the other LCA subtypes, which are recessive.
Looking back, Ashley and her mother can recall only certain emotions and the general outcome of the early years of testing. “At the time, it was just my mom and me…It was very stressful for her. I don’t really [remember] too much about it. When I ask my mom, she doesn’t really remember much either,” Ashley said. But they do recall that weathering this process was Ashley’s first step toward building resilience.
Life Level Two: Childhood
As a young child, Ashley quickly acquired skills. Living near Scottsdale, Arizona, her parents (mother and stepfather) discovered the Foundation for Blind Children (FBC). Through the FBC, as a preschooler, she began learning braille, started mobility and orientation training, and became comfortable with assistive technologies. Ashley’s parents knew her vision limitations would be challenging, so they became proactive and supportive in her future endeavors.
In kindergarten, Ashley’s vision was limited, but she was still given a certain amount of independence. She wanted to play soccer with the rest of her classmates, and her parents encouraged her to try anything she was drawn to. “All I remember about playing soccer was being hit with the soccer ball many different times,” she recalled, laughing.
She quit soccer, but took on new challenges, later trying gymnastics and dance, among other childhood activities. Although none of them worked out in the long term, Ashley credits these early activities with teaching her what she was truly capable of.
Life Level Three: Middle and High School
Ashley advocating at her retail job
Most video games feature levels that get harder as the player progresses. Life can follow a similar trajectory. Ashley recalled middle and high school as the first time she experienced significant hardships associated with her LCA. The unfortunate reality she had to face was that her vision would only continue to get worse, and seemingly in concert, kids around her got meaner. Though she was surrounded by good friends who understood her abilities and limitations, Ashley also encountered others who took advantage of them. For example, she used large-text textbooks at school, but some classmates hid them and laughed as she struggled to find them.
Ashley attended a few middle school dances but missed out on those in high school. She was unable to participate in gym classes and had to find another option. Even mobility training outside of school became loathsome because of its close proximity to her high school.
Each of these problems was compounded by constant anxiety. There was the general anxiety that afflicts many teenagers, but also the dread of becoming blind. Despite all of the hurdles, Ashley persevered. She had friends to drive her to places she needed to go. She found weightlifting, a practice that strengthened her body and deepened her relationship with accessible exercise, and fell in love with music. She began attending concerts by her favorite bands and even crowd-surfed, once making her way onto the stage. When she turned 16, she began working various retail jobs.
Through all of life’s hurdles and stresses, Ashley played video games, which became a lifeline for her. They were a bastion of comfort, yet they tested her abilities.
Life Level Four: Adulthood
Today, Ashley, now age 29, lives in a small town in Missouri with her partner, Michael, where she is facing new life challenges. She reflected on shifting from big-city life to small-town living. Near Scottsdale, she found that people were more accustomed to seeing or interacting with people with visual impairments. However, her small-town experience was more challenging. For instance, at work, she has learned to deal with customers and coworkers who do not fully understand the difference between legal and total blindness.
Ashley and partner Mykal Sandoval
“People hear the word blind or legally blind and assume it is just a black or white kind of thing,” Ashley said. “It can be frustrating. Especially when I’ve worked so hard my whole life to be where I am [with] my experience in retail and management, and it is often overlooked because of my visual impairment.”
Life Level Five: Video Gamer
The challenges Ashley faces have been made more difficult by the gradual decrease in her vision. She can no longer navigate independently outside, as bright light has made it more difficult to see, and her nystagmus and peripheral vision are worsening. While circumstances can stand in the way, Ashley won’t let them stop her. After all, she still is, and always has been, an avid video gamer, which provides a platform for her to rise to new challenges and perfect new skills.
Ashley spends her time playing retro PlayStation 2 video games like Jak and Daxter and Crash Bandicoot, as well as more modern games like Fortnite, and has streamed her gaming on the popular streaming site Twitch. She’s found a sense of accomplishment in being a talented gamer despite her visual impairment. In fact, she’s found a community of visually impaired online gamers.
Video games are a huge part of her life. While Ashley knows it might not be something she can do forever, she takes full advantage of what she can do now. The games are more than an activity. They are, instead, demonstrations of her resilience and persistence. While living with LCA can certainly present challenges, gaming has shown Ashley that it will never stop her from trying anything she sets her mind to. “I feel like my visual impairment and struggles have formed me into the person I am today,” Ashley said. “And I like that person! All of this has made me more resilient and adaptive.”
Opus Genetics has reached alignment with the US Food and Drug Administration (FDA) on the Phase 3 clinical trial design for OPGx-LCA5, the company’s emerging LCA5 gene therapy. If OPGx-LCA5 is safe and meets its primary outcome measure in the trial at six months, Opus will likely seek FDA approval by submitting a Biologics License Application or BLA. Treatment durability data at 12 months will also be considered by the FDA during its review.
Leber congenital amaurosis 5 (LCA5) is one of the rarest and most severe forms of LCA affecting approximately 5,000 globally.
The Phase 3 trial investigators plan to treat both eyes in eight patients. The trial includes a pre-treatment run-in period in which the natural history (i.e., the natural disease course) for each planned participant will be evaluated. Seven of the eight patients are currently enrolled in the run-in study. Investigators plan to begin dosing patients in the fourth quarter of 2026.
Investigators will use microperimetry, which measures retinal sensitivity at different loci (points) in the retina, as the primary outcome measure in the Phase 3 clinical trial. A mean improvement of at least seven decibels (dB) in retinal sensitivity across the central 16 test loci is considered clinically meaningful.
Opus Genetics previously reported meaningful vision improvements in three adult and three pediatric patients (aged 16-17) in its Phase 1/2 LCA5 gene therapy clinical trial at the University of Pennsylvania. Some patients saw objects for the first time after treatment. Others had meaningful improvements in visual acuity.
OPGx-LCA5 is administered by an injection underneath the retina. The gene therapy uses an engineered adeno-associated virus (AAV) to deliver health copies of the LCA5 gene into retinal cells. Researchers believe that retinal gene therapies can work for many years, perhaps the lifetime of the patient.
In reporting on emerging therapies for LCA and other retinal diseases, my mantra has always been “just the facts.” If you’re old enough, you might remember those iconic words from the stoic detective Joe Friday on the TV show “Dragnet.” Bottom line, I prefer not to embellish my reporting with hyperbole or emotion. (But I don’t wear a trench coat.)
With that said, I can’t help but be genuinely excited by the news on LCA research that came from the 2026 Association for Research in Vision and Ophthalmology (ARVO) meeting in Denver, May 3-7. Nearly 11,000 research-focused professionals from 72 countries attended this year’s meeting. Not all the LCA reports were breaking news, but collectively, the presentations and posters by researchers from all over the globe were inspiring.
Here are some clinical development highlights from the meeting:
LCA13 (RDH12): InnoVec’s emerging RDH12 gene therapy performed encouragingly at 12 months in a Phase 1/2 clinical trial in China. Ten patients (three with LCA) received one of two doses. The vision of two patients with LCA went from only hand-motion perception to modest visual acuity. Innovec is working to launch a trial for the gene therapy in the U.S. Opus Genetics also plans to launch an RDH12 gene therapy clinical trial in the US by the end of 2026.
LCA5: Opus Genetics previously reported meaningful vision improvements in three adult and three pediatric patients (aged 16-17) in its Phase 1/2 LCA5 gene therapy clinical trial at the University of Pennsylvania. LCA5 is one of the rarest and most severe forms of LCA. Some patients saw objects for the first time after treatment. Others had meaningful improvements in visual acuity. Opus is now recruiting for its Phase 3 cohort and plans to dose younger pediatric patients.
LCA4 (AIPL1): LCA4 is extremely rare and severe. At an early age, many children have only light perception or hand-motion vision. Incredibly, researchers at Great Ormond Eye Hospital and Moorfields Eye Hospital restored meaningful vision in 11 patients (aged 4 or younger) with an LCA4 gene therapy developed by MeiraGTx in the U.K. under a Specials License. MeiraGTx has licensed the LCA4 gene therapy to Eli Lilly, which is pursuing regulatory approval for it.
LCA2 (GUCY2D): Atsena Therapeutics reported 36-month results for its 15-patient Phase 1/2 LCA2 gene therapy clinical trial. Patients receiving the highest dose maintained significant improvements in retinal sensitivity and other functional measures. Furthermore, there were no serious adverse events related to the therapy. The company plans to launch its global Phase 3 cohort in the second half of 2026.
LCA10 (CEP290, IVS26 mutation): Sepul Bio continues to recruit for its global Phase 3 HYPERION clinical trial for its RNA therapy, sepofarsen. At ARVO, a post-hoc, paired-eye analysis of the previous Phase 3 ILLUMINATE clinical trial for sepofarsen was presented. It showed that treated eyes performed better than untreated eyes in the same patient. Why is this important? In the original ILLUMINATE clinical trial, the treated eyes of patients were compared with untreated eyes in a different patient cohort (i.e., a control group). Ultimately, ILLUMINATE, completed in 2022, didn’t meet its primary endpoint. The good news: HYPERION uses a paired-eye design, which researchers believe can lead to a stronger efficacy signal and a better opportunity to meet the primary endpoint.
This is by no means an exhaustive list of ARVO research presentations on LCA. Please feel free to reach out to me at ben@hopeinfocus.org if you have any questions about these or other projects.
PAO’s Intermediate group with speaker Rob Long, Executive Director of Uplifting Athletes
The Sanford Research Center hosts the largest registry in the U.S. for patients with rare diseases, primarily children. Work done at Sanford Research led to the first-ever clinical trial using gene therapies for one of these diseases. PPALS provides an environment where conversations and collaborations with industry and other patient advocacy organizations can happen naturally. The training provides opportunities for connected conversations in a small-group setting.
This is Eve’s second year, joining the intermediate course in the Patient Advocacy Organization (PAO) group. “I am excited to be involved again with PPALS and meeting other people who help push for treatments, engage in advocacy, and provide resources for our community,” Eve said. “I’ve learned more about the industry and gained a comprehensive understanding of our space, while building connections within the rare disease community to bring new information, ideas, and opportunities back to Hope in Focus.”
One session that stood out to Eve was “Fundraising and Beyond” led by Terri L. Klein, CEO and President of the MPS Society. Klein discussed the MPS Society’s work and explained how various fundraising and community engagement strategies can effectively support and grow patient advocacy organizations. The session also gave PAO participants the opportunity to strategize together and discuss ways to better connect with and support their communities.
Experiences like PPALS continue to help Hope in Focus expand its connections, strengthen advocacy efforts, and bring valuable resources to the rare disease community.
LCA5 is a rare inherited retinal disease causing blindness or severe vision loss in childhood.
The RDEP process can allow potential FDA approval based on one adequate and well-controlled study plus additional robust confirmatory evidence, which may include: strong mechanistic or biomarker evidence; evidence from relevant non-clinical models; clinical pharmacodynamic data; and case reports, expanded access data, or natural history studies.
OPGx-LCA5 is currently being evaluated in a Phase 1/2 clinical trial at the University of Pennsylvania. Vision gains and positive safety results for the treatment for adult and pediatric trial participants have been reported. Enrollment for an adaptive Phase 3 clinical trial is ongoing. OPGx-LCA5 has also received Rare Pediatric Disease, Orphan Drug, Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA.
Over the years, I’ve learned that most people don’t understand that visual impairment is a spectrum. Most people think there are three options: 20/20 vision, vision that can be corrected by glasses, or total blindness.
As a child, I passed as fully sighted in most situations. When I told people that I was visually impaired, their first question often was, “Why don’t you wear glasses?” After getting a guide dog, I get fewer questions like that; however, people now assume that I am totally blind.
20/20 Vision
When people know what you can see, you are more likely to experience environments where you feel included. This is why it is so helpful to be able to explain what you can and can’t see in simple terms. It’s also important to take the initiative to share this information.
I describe my vision as looking backward through binoculars while wearing several pairs of sunglasses. This lets people know that things look much smaller to me, that I can’t read printed text, and that I can’t see in dark/dim lighting. It is much more effective to use this analogy than to list things I can’t see.
Sharing my analogy also helps someone to imagine what it would be like to look through binoculars backwards, wearing several pairs of sunglasses. But they often can’t imagine what it is like not to see in dim lighting. It is also hard for some people to ask what I can and cannot see since they don’t want to highlight my limited vision or are just uncomfortable asking.
Jack’s Vision
Providing information about your visual impairment or offering an analogy often puts people at ease. When people know you are comfortable talking about it, they feel freer to ask questions.
Imagine playing cards with a new group of friends. One person at the table asks, “Will you be able to play cards with us?” You know you won’t be able to see the cards in the center of the table, but you share your vision impairment analogy or description. By helping your friends understand that you can see the cards in your hand but will need them to announce the card that they lay down, allows them to make simple accommodations so you can participate. Because you were able to describe your vision loss simply, you and your friends had a great evening together.
I encourage you to come up with your own analogy to describe how you see. I know I am not alone in worrying about the accessibility of new environments. Most people are happy to do what they can to make things more accessible. Helping them understand what you can see will help them help you and lead to a more fulfilling, connected life.
Amanda Geffre gripped the steering wheel of her car as she fought back tears. The two-hour trip home from Fargo, ND, with her two-year-old daughter, Pepper, felt far longer than the trip from their home in Oakes earlier that day. Pepper’s appointment with the Fargo pediatric ophthalmologist was supposed to be for updated glasses or maybe bifocals. Amanda hadn’t expected new information, and her mind now churned with the implications of the doctor’s observations.
The Geffre Family
She called her husband, Jordan, struggling to find the words to explain what the doctor had said: Pepper had permanent vision loss and damage to her retinas. “I was confused and in shock. The doctor mentioned grieving, but I couldn’t grasp what he meant,” Amanda recalled.
For several years, the Geffres had been trying to uncover what was impeding their daughter’s development. “When we discovered that she had some vision loss, we hoped that glasses and the state’s early intervention program would meet her needs,” Amanda said. “We never expected a diagnosis of a rare genetic condition.”
Early Questions and Uncertainty
Connor, the Geffres’ first child, was born in 2014 and met all his milestones. But when Penelope (“Pepper”) arrived in 2017, Amanda and Jordan quickly noticed she lagged behind. “When she was about six months old, our pediatrician told us she should be evaluated,” Amanda said. “At 11 months, she wasn’t crawling, and she qualified for early intervention. But we still didn’t know the cause.”
Pepper disliked getting dressed and had separation issues when she couldn’t hear Amanda’s voice. “She also avoided physical activities or touching things,” said Amanda. “We wondered if she had hearing, or balance problems, or maybe a sensory disorder.”
Pepper’s inconsistent behaviors made it difficult to pinpoint a cause. For example, when she started eating finger food, sometimes she’d grab it right away, at other times, Amanda would have to tap on the tray or point it out before she’d find it. If she dropped a toy, she might have a hard time locating it, but not always.
When Amanda mentioned these behaviors to the early intervention team, they suggested she might need glasses. An appointment with a local eye doctor, when she was about 18 months old, confirmed that need. “Once she had glasses, Pepper started walking, and we thought the problem was solved,” Amanda recalled. “But she continued to trip or walk into things. It seemed like the glasses weren’t working, and we felt that something wasn’t right.” It was then that their local eye doctor suggested a stronger prescription or bifocals and referred Pepper to the pediatric ophthalmologist in Fargo.
On the Road…Again
Much to Amanda’s surprise, the pediatric ophthalmologist said a new prescription was the least of his worries. “He said Pepper had vision loss and that her retinas weren’t healthy,” Amanda explained. “He also wanted to schedule a brain MRI to see if something brain-related might be causing her vision loss.” Although it felt somewhat contradictory, the couple hoped the MRI might reveal something that could restore Pepper’s vision. But the test was clear, and the conclusion was that their daughter’s vision loss was genetic.
The next referral was to a specialist in the Twin Cities (Minneapolis/Saint Paul, MN). That specialist wasn’t concerned, saying that Pepper had moderate vision loss. But he wanted to evaluate her retinal function with an electroretinogram (ERG). Unfortunately, the test was delayed by the COVID shutdown.
“Pepper had the ERG somewhere between ages two and three,” said Amanda. “Afterwards, the doctor said he was worried about her vision and that we should connect with the North Dakota School for the Blind. He told us genetic testing was expensive and he didn’t think it was necessary.”
Genetic Testing
Fortunately, their local eye doctor was able to arrange for free genetic testing, and Pepper was subsequently diagnosed with the recessive IQCB1/NPHP5 mutation that causes Leber congenital amaurosis (LCA11). In addition to vision loss, this mutation can cause end-stage kidney failure.
“Getting Pepper’s LCA diagnosis consumed me,” Amanda said. “It was all I could think or talk about. I Googled everything. No one could tell us what her vision might eventually be like.”
Amanda and Jordan underwent genetic testing to determine whether they were carriers or whether Pepper’s LCA was due to a spontaneous mutation. “When we found that we were carriers, I was in my second or third trimester with our son, Jade,” Amanda said. “We now knew that he had a 25 percent chance of having LCA.” Jade, tested soon after his birth in 2021, did not have LCA.
Pepper Geffre
Pepper’s Progress
The support from the state’s early intervention program and vision services was key to Pepper’s development. “I was so relieved when she started walking and using a kind of rolling plastic rectangle that they provided,” said Amanda. “She could move and run because she understood that this thing he was pushing would detect if there was something in the way. It really helped her developmentally.”
Then, just before Pepper turned three, their school district opened a special education preschool. Amanda said it was a battle for Pepper to qualify because the division teacher didn’t understand her diagnosis or the extent of her vision loss. Once that problem was rectified, she qualified and began learning Braille and how to read and write.
As time went on, the Geffres grew comfortable with Pepper’s development. She began using a cane and was telling her parents what was and wasn’t working. “She was doing so well in school, we kind of forgot that we had a risk of LCA if we had another child.”
Baby #4…
Maverick Geffre
Pregnant with their fourth child, Maverick, the Greffes faced the possibility that this baby could have LCA. “I told myself if it happened again, we knew what to do, who to contact, and who would need to work with this child,” Amanda said.
Maverick was born in 2024 and was diagnosed with LCA11. “Even though we were somewhat prepared, it was still very hard,” recalled Amanda. She called the early intervention team and vision services, and Maverick qualified right away.
Although Maverick’s vision was better than Pepper’s, he still had developmental delays. “I was a little disappointed since I hoped that by starting him early, he wouldn’t be as delayed. He was still not walking at 17 months, even though he had gotten glasses at four months old,” Amanda said. “But his physical therapist said that a child with visual impairments is going to be delayed and will have a different developmental timeline.”
When Maverick was about six months old, the Geffres took him to the same pediatric ophthalmologist in Fargo who had seen Pepper. But their visit was confusing. “He didn’t think the genetic test was correct and said that Maverick’s retinas looked fine, and that maybe he had retinitis pigmentosa. That made us wonder if his genetic testing could have been messed up,” Amanda said.
Finding Clarity
A turning point occurred when the Geffres met another family in North Dakota with a son who had LCA, and their recommendation provided Amanda and Jordan with a vital resource. “They were seeing a specialist in retinal diseases in Philadelphia, and encouraged us to see him,” Amanda said. “I wasn’t sure if he would see Maverick because he was so young, but we really needed someone to tell us what was going on! So, we reached out to the specialist in Philadelphia, and he said he would see an infant.”
Both children were evaluated by Tomas Aleman, MD, of the Scheie Eye Institute, which is part of Penn Medicine at the University of Pennsylvania. “He said that Pepper and Maverick had the most vision of children with LCA that he has seen to date. That was somewhat comforting, knowing that at this point they are on the low end of the spectrum and are pretty fortunate,” Amanda said.
Pepper, Jade, Connor, and Maverick
The Geffres know that both children will have more vision loss, but for now, they take comfort in knowing that their children’s diagnosis is accurate. “Dr. Aleman explained that vision loss with LCA11 is generally a slow progression with loss and then a period of stability.” Because LCA11 can also cause kidney failure, both children are being regularly monitored via bloodwork and ultrasound.
Life in Motion
The entire family, including Amanda’s parents, attended the Hope in Focus Family Conference this past June. “It was so good! My kids really enjoyed it, and we met another family with a daughter who has LCA and lives in Iowa. She is two or three years older than Pepper, but they made a connection and have been talking,” Amanda said. “It’s been great for Pepper because she feels like she has an older friend, and they have the shared experience of LCA.”
Despite the Geffres’ initial frustrations, the family is forging ahead. Bright-colored tape marks the stairs and other obstacles in their home. It is an ongoing challenge to keep the furniture in the same place — their energetic children, Connor (age 11), Pepper (age 8), Jade (age 4), and Maverick (age 1), love rearranging it. Everyone is adjusting and adapting to the unexpected challenges and joys that arise in a family living with LCA. “We don’t know exactly what the future holds, but we’re facing it together,” said Amanda.
I am excited to report on impressive progress in the development of Odylia Therapeutics’ emerging gene therapy for retinal degeneration caused by RPGRIP1mutations, which is most often diagnosed as LCA6. Like the journey for so many inherited retinal disease treatments and the companies that develop them, there’s a long story here ⎯ a story of commitment, resourcefulness, and persistence. I’ll touch on that in a moment, but I encourage you to learn much more from an enlightening Hope in Focus podcast interview I conducted with Ashley Winslow, PhD, chief executive officer at Odylia, on March 3rd. It’s an excellent episode, if I do say so myself.
Background on RPGRIP1-associated disease
The RPGRIP1 protein is critical for the structural development of photoreceptors (rods and cones) and the trafficking of important proteins. Remember, photoreceptor cells are long, thin, light-sensing cells in the retina that enable us to see, and many different proteins need to move up the length of the cells for them to work properly and survive long term. That movement is called trafficking.
Also, remember that genes are like recipes for proteins. Cells read genetic messages to make proteins, and ultimately, it’s the proteins that are critical to our cells’ function and survival. In the LCA6 case, if there are spelling mistakes (i.e., mutations) in the RPGRIP1 gene, there isn’t sufficient RPGRIP1 protein produced, and photoreceptors suffer.
Mutations in the RPGRIP1 gene cause LCA6 but can also be associated with milder forms of retinal disease, such as cone-rod dystrophy (CORD), retinitis pigmentosa, or achromatopsia. Though LCA6 usually causes significant vision impairment at birth, photoreceptors can potentially survive into young adulthood, thereby providing a wide treatment window for patients.
The RPGRIP1 gene therapy story
Initial development of Odylia’s gene therapy began at Mass Eye and Ear (Harvard) more than 15 years ago. Researchers there demonstrated efficacy for gene therapy in mouse models. With sustained funding from Odylia, the RPGRIP1 gene therapy has moved into a safety and toxicology study, a critical step before moving into a clinical trial. The study will also help researchers determine the optimal dosing range for the trial. Also important, Odylia has clinical manufacturing in place and received positive feedback from the FDA on the trial design. However, additional funding is needed to launch the trial.
Odylia also has gene therapy programs underway for vision loss due to mutations in the USH1C and NPHP1 genes, which are in preclinical development.
The Odylia story
Odylia was formed in 2017 as a nonprofit collaboration between Scott Dorfman, a father of two children with Usher syndrome 1C, and gene-therapy pioneer Luk Vandenberghe, PhD, of Mass Eye and Ear. Their goal: Provide the commitment and resources needed to advance rare disease treatments into early-stage clinical trials. In the podcast, Ashley Winslow, PhD, Odylia’s chief executive officer, said that as a nonprofit, Odylia has a stronger commitment to rare disease therapy development than a typical for-profit biotech or pharmaceutical company that’s focused on minimizing financial risk and maximizing revenue. By de-risking therapies through early-stage development, Odylia aims to attract investment partners (i.e., for-profits) to its programs.
Dr. Winslow explained that the key to Odylia’s success is its collaboration with patient groups, academic researchers, manufacturers, and clinical research organizations to find a way forward both in fundraising and therapy development. “In the rare disease space, you have to think about the science and the fundraising hand in hand because financial resources are often limited,” she said.
If you’re interested in learning more about Odylia and its emerging therapies, you can reach out to Dr. Winslow at awinslow@odylia.org.
In May 2025, Johnson & Johnson (J&J) announced that though its emerging gene therapy bota-vec for X-linked retinitis pigmentosa (XLRP) improved vision for many patients in its Phase 3 clinical trial, the gene therapy didn’t meet its primary endpoint. Not meeting a primary endpoint in a clinical trial is not good news even when overall results are favorable.
So, the question became: Will J&J seek regulatory approval for bota-vec or perhaps continue clinical development for it? Many of us in the inherited retinal disease (IRD) community were not optimistic. We were afraid bota-vec development was finished and the treatment would never make it out to patients who so desperately needed it.
But today I am pleased to say that hope is alive for bota-vec. On April 16, 2026 ⎯ nearly a year later ⎯ MeiraGTx, the original developer of bota-vec, announced it is acquiring the bota-vec license from J&J. MeiraGTx plans to seek regulatory approval for the gene therapy in the US and EU. If approved ⎯ and that’s still a big if ⎯ bota-vec could be available to patients in 2027.
We applaud MeiraGTx ⎯ a Hope in Focus partner and developer of a vision-restoring gene therapy for LCA4 (AIPL1 mutations) ⎯ for giving new life to bota-vec. It was a bold move, no doubt. And, we applaud the many advocates in the IRD community ⎯ including researchers, patient groups, and families ⎯ for being strong voices in support of bota-vec advancement. Our voices were heard.
The important take-away message for all of us in the IRD and LCA communities is to stay tenacious, stay resilient, and continue to do our best in moving the research forward.
