Science Education Archives

Diverse Emerging Therapies Featured at the 2025 Hope in Focus Conference in Minneapolis

The development of diverse treatment approaches for Leber congenital amaurosis (LCA) is necessary because no single modality will work for everyone affected. While development of gene augmentation therapies (i.e., replacing mutated genes with healthy genes) has much momentum, other approaches also show promise as they move into and through clinical trials. Three of those emerging alternatives were discussed by a panel of experts at the Minneapolis meeting in June. The panel was moderated by Amy Laster, PhD, chief scientific officer, Foundation Fighting Blindness.

Ray Therapeutics’ Optogenetic Approaches

Raj Agrawal, MD, the vice president of clinical development at Ray Therapeutics, presented his company’s emerging optogenetic therapies which are moving into clinical trials for retinitis pigmentosa (RP), choroideremia, Stargardt disease, and age-related macular degeneration. While Ray isn’t currently targeting LCA, optogenetics is an approach which may be applicable to some LCA patients.

Optogenetics is a gene-independent approach for restoring some vision for people with advanced inherited retinal diseases (IRDs) who have lost most or all their photoreceptors (rods and cones), the retinal cells that make vision possible. Ray’s therapies deliver genes that express a light-sensing protein called channelrhodopsin to either bipolar or ganglion cells ⎯ cells that are normally not light sensitive but survive after photoreceptors are lost. In essence, the therapies enable bipolar or ganglion cells to work like a back-up system for photoreceptors. The therapies are delivered by a one-time injection into the vitreous, the soft gel in the middle of the eye. These non-invasive injections are performed thousands of times every day in retinal doctors’ offices for treatment of AMD and diabetic retinopathy.

While Ray’s clinical trials are at an early stage, Dr. Agrawal said early reports for safety and efficacy have been encouraging. Stay tuned.

Sepul Bio’s RNA Therapies for LCA10 and USH2A

In early 2022, the biotech company ProQR reported that sepofarsen, its RNA therapy for LCA10 (IVS26 mutation in CEP290), did not meet its primary endpoint in a Phase 2/3 clinical. That news came despite vision improvements, some significant, for many patients in the trial. The endpoint miss led ProQR to stop development of its ophthalmology assets ⎯ sepofarsen and ultevusen (exon 13 mutations in USH2A) ⎯ and find a company to acquire them.

Mike Schwartz, who was then vice president, global project leader, at ProQR, said, “That was devastating for me, the doctors, and the patients.” He noted that one patient with LCA10 in the trial with only light perception gained enough vision after receiving sepoafarsen to see letters on an eye chart. Another LCA10 patient in the study was able to return to his work as a carpenter after treatment.

Fortunately, a year and a half later, the large European eye care company Théa acquired sepofarsen and ultevursen and formed the Sepul Bio business unit to move the therapies back into clinical trials. Many former ProQR staff went to Sepul Bio including Dr. Schwartz who is now their chief operating officer.

A Phase 2 clinical trial for ultevursen is underway and a global Phase 3 trial for sepofarsen is imminent. Using what was learned from the ProQR trials, the Sepul Bio team made significant changes to designs for the forthcoming trials ⎯ changes they believe will greatly improve chances for success. Mr. Schwartz thanked the Hope in Focus team for providing input from patients for the sepofarsen clinical development program.

Sepul Bio’s RNA therapies, known as antisense oligonucleotides (ASOs), are tiny pieces of genetic material that fix mutations in RNA, the genetic messages that cells read to make protein that’s critical to the cells’ health and function. Both sepofarsen and ultevursen are delivered by intravitreal injections every six months.

BlueRock Therapeutics’ Photoreceptor Replacement Therapy

The development of cell therapies for IRDs has been challenging for numerous reasons. Therapeutic cells haven’t been easy to source and enabling them to survive and integrate when transplanted into patients’ retinas has been difficult.

As a panelist for the session, I had the privilege of discussing a promising photoreceptor replacement therapy from BlueRock Therapeutics which came out of the lab of stem cell pioneer David Gamm, MD, PhD, University of Wisconsin-Madison. Excitingly, BlueRock’s therapy just moved into a clinical trial for people with RP and cone-rod dystrophy. Dr. Gamm said the cells might at some point be relevant to LCA patients.

The photoreceptor precursors used in the trial came from induced pluripotent stem cells (iPSC). The iPSC were derived from a small sample of mature blood or skin cells from a healthy donor. The cells were genetically tweaked to revert back to a stem cell state. The iPSC were then coaxed forward to develop into the photoreceptor precursors. As precursors, they aren’t fully mature. Dr. Gamm research showed that precursors have the best chance at survival and integration after transplantation.

BlueRock has the backing of two prominent companies: Bayer and Fuji Film. The Foundation Fighting Blindness funded Dr. Gamm’s previous iPSC-related lab research.

The BlueRock trial is moving forward methodically so that investigators can ensure safety for patients and best understand which patients and conditions can benefit most from the approach.

Living with IRDs: Insights and Inspiration from the Front Lines

The 2025 LCA Family Conference in Minneapolis, MN, offered four informational panel sessions, where the 135 attendees learned about living with Leber congenital amaurosis (LCA) and other inherited retinal diseases (IRDs), participating in clinical trials, and the latest research and therapy updates.

The first session, “Living with an IRD,” was moderated by Laura Manfre, co-founder and Board Chair of Hope in Focus. This session is often a highlight for families wanting to learn how to support their children diagnosed with an IRD.

Laura Manfre, Lee St. Arnaud, Elle St. Arnaud, Jack Morris, Leslie Morris

Laura posed questions to the four panel participants, which included 18-year-old Elle St. Arnaud, who has LCA IQCB1/NPHP5 and is attending Boston University this fall, and her father Lee St. Arnaud, and 22-year-old Jack Morris, who has RP CRB1 and is a recent graduate of Brown University, and his mother Leslie Morris.

Below are some of the panelists’ edited responses to Laura’s questions.

What has your school journey been like? What challenges have you faced, and how did you advocate for yourself?

Elle St. Arnaud

Elle was educated in the public schools with a paraprofessional supporting her in class from preschool through fourth grade. She said that a key to her success was learning to advocate for herself early on by participating in her individualized education plan (IEP) meetings, explaining her accommodations to teachers, and taking responsibility for communicating her needs, especially regarding her vision. Elle reflected on the importance of self-advocacy and how it has shaped her life.

“It’s vital for kids to be able to explain their accommodations, as others often don’t fully understand visual impairments,” she said. “While I’ve had positive experiences, I’ve also faced challenges, such as being discouraged from joining the debate team or taking advanced classes. I pursued both anyway, proving that being blind doesn’t limit one’s ability to succeed. Self-advocacy and standing up for your needs are essential life skills.”

Jack Morris

Jack started in public schools and later switched to a private school. His vision was relatively good throughout most of his schooling. Jack thought he might have done even more to advocate for himself. Still, regular meetings with teachers and advisors proved very helpful. He said, “When people understand what you need, they generally want to help.” Although at the university level, he said some professors were resistant to making accommodations.

He stressed that “Accommodations are not favors—they are necessary for success. Blind individuals are not less intelligent; they simply need equal access to materials to perform just as well as others. Having confidence in advocating for these needs is crucial, and legal protections like the ADA support this.”

As parents, can you share a little about your journey? How was it seeking a diagnosis, and what are some things you wish you’d known earlier?

Lee St. Arnaud

Lee explained that Elle and her older brother, Patrick, both have LCA. When trying to diagnose Patrick’s vision issues, he shared how difficult it was when the doctor offered only a brief response, instructing them to return in five months to confirm their son’s blindness. Overwhelmed, the family immediately reached out to resources like the Chicago Lighthouse for the Blind, which connected them with supportive networks and foundations.

Lee stressed the importance of parents being proactive and finding tools like a detailed year-by-year visual goals guide, which they used effectively in IEP meetings to advocate for their children’s needs. He emphasized the importance of being prepared, pushing for necessary services, and actively advocating for the child and family.

The St. Arnauds encouraged their children to participate in outside activities like adaptive climbing and the live hockey association. “So many times we were nervous and sweating bullets. But by the time we got done, the kids were like, you know what? We can do this!” Lee said.

Leslie Morris

Leslie said that Jack’s diagnosis with a recessive form of RP at age five came as a shock because there was no family history. She described feeling heartbroken and overwhelmed by a sense of loss and isolation. Despite these emotions, Leslie and her husband, Jason, chose not to accept discouraging responses from doctors. Instead, they took action—connecting with others affected by IRDs and becoming involved with the Foundation Fighting Blindness, where both serve as trustees.

Advocacy became like a second job for the Morris family, as they worked to ensure Jack had every opportunity for a full and meaningful life. Leslie said they didn’t want the disease to define their son, and they encouraged him to try various activities like baseball, football, swimming, wrestling, and guitar. “We focused on letting Jack decide when to step away from activities while gently steering him toward pursuits that offered long-term fulfillment,” Leslie said.

How do you give your child enough independence to grow and to learn, while also wanting to protect and keep them safe?

Lee St. Arnaud

Lee felt that they didn’t experience significant disagreements with Elle or Patrick regarding their ability to self-manage. He stressed the importance of balancing caution with encouragement and supporting early opportunities for independent experiences in the community without rushing the process. He also reflected on the importance of understanding your child’s interests as they mature.

Elle St. Arnaud

Elle immediately spoke up after her father, expressing her childhood frustration and conflict with her parents over having to take Orientation and Mobility (O&M) training particularly the inconvenience and social discomfort of being taken out of school. Despite hating it at the time, she admitted the lessons had long-term value, especially in promoting independence. She noted the importance of starting children early with independent tasks at home, like cooking and laundry, while pacing community-based skills more carefully. “I think parents should keep their children engaged in O&M even if the child resists,” Elle said. “Because it equips them with critical life skills—such as safely crossing the street—that pay off later.”

Leslie Morris

Leslie emphasized the importance of parental teamwork and unity, particularly when supporting a child’s journey toward independence. She admitted to being a bit of a helicopter mom. “My husband, Jason, and I agreed on things before letting Jack go out and try them,” she said. “Having somebody by your side through this journey is very important.” She added that when parents are aligned in decisions and approaches, it helps minimize conflict and makes the process smoother.

Jack Morris speaking at the 2025 LCA Family Conference

Jack Morris

Jack didn’t recall having major conflicts and expressed gratitude for the trust his parents placed in him. One slight regret he had was not wearing sunglasses earlier, due to self-consciousness. Jack said he appreciated the opportunity to try things—even fail—while still feeling supported and safe.

Much to the amusement of the conference attendees, Jack recounted a brief period when he was legally allowed to drive, a decision made with medical guidance that, in hindsight, seemed very questionable.

“I appreciated that my parents trusted me to be able to take care of myself. This journey makes you resilient, tough, and resourceful,” Jack said. “Kids can be very clever in planning solutions to their unique circumstances, and my parents trusted me in that.”

Community members have expressed that mental wellness and accepting vision loss can be difficult. Elle and Jack, what are your thoughts?

Elle St. Arnaud

“Not wanting someone to see your pain and not wanting to wear sunglasses or use a cane will likely peak around middle school,” Elle said. “No one wants to be different, and you want to be ‘on trend’ with everybody else.”

She added that having a para in the classroom with her all of the time was an inhibitor and made it harder for her to talk with other kids. “Parents should try not to hover when their child is with other children because it can make them feel less confident or social,” she said.

Elle said she made it a priority to share her experiences as a blind person with her sighted friends. “We’d make jokes about it, and I talk about it constantly. I’d share what I’ve experienced and every blind story I’ve had,” she explained. “I think that’s important because when you need to ask your friends for help, they are a lot more understanding because you’ve explained it and talked about it so many times with them.”

For example, she told her friends about walking into a door, which helped them be more aware that she might not see it, allowing them to take the initiative to guide her when needed. “I think the easiest way to be accepted is to talk more about your blindness so it feels more normal,” Elle said.

Jack Morris

“I think there’s a line to be found between letting a disease define you and rejecting that it’s a part of you, because retinitis pigmentosa (RP) has been a huge part of my story—a beautiful but also a tough part. It’s something that feels different and lonely, but also unifying and community-building,” Jack said. “If we can find ways to live in and with our disease rather than despite it, that’s where truth and freedom lie for me.”

He offered advice to parents, saying that they needed to be strong in ways that aren’t obvious. “One of the hardest things for parents is watching their child struggle. But sometimes the biggest strength is allowing them to struggle. Kids need to feel the full spectrum of emotions—challenge, loneliness, empowerment, and togetherness,” Jack said. “If parents can be there as a foundation, even when things are hard, and let them be hard before stepping in with action, that’s one of the most powerful and meaningful things they can do for their children.”

Moving Forward: Understanding More about Clinical Trials

The second panel session of the 2025 LCA Family Conference, “Participating in a Clinical Trial,” examined clinical trial development and participation from the researcher and patient perspectives. This session supports a goal of Hope in Focus to educate the Leber congenital amaurosis (LCA) community so members are ready to participate in clinical trials when opportunities occur. For researchers, informed and prepared LCA patient groups are critical to moving a new drug or therapy through the testing pipeline.

Ben Shaberman, vice president of Science Communications at the Foundation Fighting Blindness, was the moderator. The panelists were Tomas Aleman, MD, a researcher with over 30 years of experience in researching genetic therapies related to inherited retinal diseases (IRDs), and Sarah McCabe, a mother and teacher from Iowa, and an LCA individual with the RPE65 gene mutation. Sarah participated in a gene therapy study in 2007, and 14 years later was treated with LUXTURNA®.

Overview of the Research Process

Ben began with an overview of the drug development process, highlighting that it is complex, demanding, and lengthy—often taking 10–15 years, and costing tens of millions of dollars. For retinal diseases like LCA, the development of a drug or therapy begins with identifying and understanding the mutated gene causing the degeneration. Researchers study these genes and their effects on the retina, then create disease models—traditionally in mice, but now also using “mini-retinas” grown in dishes.

Conference attendees listening to the “Participating in a Clinical Trial” panel session.

Transitioning from animal or lab models to human trials is a significant hurdle, requiring higher-quality manufacturing standards, regulatory compliance (e.g., FDA), considerable funding, and specialized expertise. “This phase, called translational research, is often referred to as the ‘valley of death,’ Ben said. “Because many therapies fail to progress to clinical trials.”

For LCA, gene therapies can take 5–8 years to develop. Researchers must determine the right therapy, dosage, and method of administration before progressing to clinical trials, which can last 6–8 years, are extremely expensive, and often pose challenges for researchers and patients. While the process is rigorous and time-consuming, it is critical for developing effective therapies.

LCA Gene Research

Tomas Aleman, MD, co-directs the Center for Hereditary Retinal Degenerations (CHRD) at the Scheie Eye Institute at the Perelman School of Medicine, University of Pennsylvania. Dr. Aleman’s groundbreaking work has transformed the treatment of LCA, becoming the first disease where gene editing techniques were applied and gene therapy successfully restored vision. “Unlike what many people believe, most LCA patients are not completely blind, and their retinas often remain structurally intact,” Dr. Aleman said. “This makes the condition an ideal candidate for experimental therapies.”

Early research focused on RPE65-related LCA and started with animal models, including a dog, that helped pave the way for clinical applications, eventually leading to the first successful human treatments. After a decade of preclinical research, Dr. Aleman’s team moved into human trials, with LCA patients like Sarah McCabe playing a vital role. Dr. Aleman stressed the essential role of patients in clinical trials, saying that “Patient feedback is often critical to recognizing early signs of success.”

Clinical trials present both opportunities and challenges. They require long-term patient commitment and rely heavily on funding from smaller biotech companies. Patient selection for trials is also strategic—those chosen typically have structurally preserved retinas with poor function, maximizing the likelihood of measurable improvement. Dr. Aleman emphasized that exclusion from a trial does not mean the therapy won’t eventually be available for an individual; rather, it reflects the strict criteria needed to answer key safety and efficacy questions.

Looking ahead, Dr. Aleman said the goal is to expand the proportion of treatable LCA forms from roughly 25 percent to 50 percent. The progress made so far demonstrates the transformative potential of gene therapy in restoring vision for patients with inherited retinal diseases.

Doing Gene Therapy

Dr. Aleman gave an in-depth explanation of the gene therapy process for treating inherited retinal diseases, particularly focusing on subretinal delivery techniques. Gene therapy in this context is a meticulous process where the therapy is delivered directly beneath the retina via a subretinal injection.

Performed under general anesthesia, the injection only takes 5–10 minutes. It is done by entering the eye through three small incisions, removing the gel-like vitreous, and using a hair-thin needle to deliver the gene therapy. According to Dr. Aleman, the surgery resembles retinal detachment repair—a well-established procedure.

While there is an alternative delivery method known as intravitreal injection that is less invasive, it has not proven to be as effective or safe for all retinal indications. In particular, immune detection can reduce the efficacy of intravitreal injections, whereas subretinal injections can bypass these mechanisms.

Following surgery, a rigorous monitoring process begins to assess the treatment’s safety and effectiveness. This process includes frequent follow-up visits in the early stages—often at one, three, and six months and a year—during which visual function is tested and retinal imaging is conducted.

Participation in gene therapy trials is entirely voluntary, and patients can choose to withdraw at any time. However, once the gene therapy is delivered, it cannot be undone. The therapeutic genes remain in the eye’s cells indefinitely, making informed consent and long-term commitment critical components of the clinical trial process.

Patients are typically monitored for at least two years, and in many cases, much longer. For example, in the case of one early trial (the RPE65 trial), patients have been followed for over 16 or 17 years. Dr. Aleman emphasized that there is a lifelong partnership between patient and physician, stating that monitoring continues for as long as possible, regardless of whether the formal trial period has ended.

Dr. Aleman hopes to move toward treating very young children, ideally before age two, since the brain’s ability to learn to see develops rapidly in infancy and early childhood. Early treatment is believed to yield better visual and developmental outcomes, supported by early rehabilitation and educational interventions. A grant received two years ago is helping to support research and clinical work toward this goal.

“While gene therapy offers transformative potential, it also requires thoughtful implementation, long-term follow-up, and a commitment to tailoring support beyond the surgical intervention,” said Dr. Aleman. “The mission is not only to restore vision but to improve the quality of life and long-term outcomes for patients, especially children, by intervening as early as possible.”

Sarah’s Story & Clinical Trial Experience

When Sarah was about 10 days old, her mother, an ICU nurse, noticed that she wasn’t following the developmental patterns she’d observed with her son. Concerned, they visited a pediatrician who suspected something was wrong with Sarah’s vision. Further evaluation by a neurologist ruled out any neurological issues, and her parents were assured that Sarah would hit developmental goals right on time.

Regular eye exams ensued, with her parents keeping detailed records of each visit. Eventually, Sarah was referred to the University of Iowa, where tests suggested LCA, but at that time, genetic testing wasn’t available. A definitive LCA genetic diagnosis (RPE65) was finally made when she was in eighth grade.

At age 19, she was recruited for a clinical trial after struggling with vision during college. After going through the initial interviews and assessments, she was approved as a clinical trial participant. Sarah said the doctors clearly explained all the details and risks of the trial and that it was an experimental procedure primarily aimed at testing safety. The decision whether to move forward was left to Sarah and her family. “There wasn’t a whole lot of talking with my parents about it,” she said. “We knew things weren’t going to get any better if I didn’t participate, and I could be a part of helping [research advance].

To facilitate Sarah’s participation in the clinical trial, logistics were carefully arranged around her college schedule. It was toward the end of her senior year that her family drove her from Iowa to the University of Florida, where she underwent her first gene therapy surgery at age 23, describing it as terrifying but perfect.

The pre-operative steps included bloodwork and other standard preparations. During the surgery, Sarah was awake—a protocol that has since changed, with patients now put under general anesthesia. Post-surgery, she had a significant moment when she was able to read a giant letter “A” on a card, confirming that the surgery hadn’t worsened her vision. Over time, she noticed a new visible area in her field of vision, referred to as a “headlight,” which was a significant improvement.

Sarah’s recovery involved staying in Florida for a month with her family, with frequent follow-up visits stretching out from monthly to annually. Her clinical trial team remained in contact with her years after the trial formally ended. Fourteen years later, after LUXTURNA® was FDA-approved, she received the gene therapy at the University of Iowa, which improved her vision. Now in her 40s, Sarah’s primary goal is to maintain the stability of her vision. She summarized her clinical trial and gene therapy experiences, saying, “It was a long time ago now, but it was a very cool experience. All of it!”