Genetic Tests Glean New Diagnoses for People Living with Rare Inherited Retinal Disease

Three people who received diagnoses of Leber congenital amaurosis (LCA) in recent years – but lived most of their lives thinking they had retinitis pigmentosa (RP) – gave us the opportunity to hear their stories at a special session of the VISIONS 2022 conference this summer.

An RP diagnosis is currently given to patients with photoreceptor degeneration but good central vision within the first decade of life; an LCA diagnosis is given to patients who are born blind or who lose vision within a few months after birth.

In the middle of a two-day conference hosted by the Foundation Fighting Blindness, several of us from Hope in Focus in an LCA Mix & Mingle session heard about the sometimes-rocky road to getting a confirmed genetic diagnosis of a rare inherited retinal disease (IRD), especially in the years before access to genetic testing.

Ultimately, though, that difficulty did not hold back these individuals from creating happy and productive lives because they did not allow their blindness to define them.

A college of Linda, Russ, and Emily. — Linda Joy Wirth, Russ Davis, and Emily Townsend Cobb

Linda Joy Wirth

Blind since birth, Linda Joy Wirth, now 75 and living in Lakewood, Colo., was diagnosed with RP in the 1960s. Because she was told from an early age that nothing could be done for her blindness, she stopped thinking about her diagnosis and focused on her education, marriage, and children.

Then she thought: “You can never cure something if you can’t diagnose it.”

In the 1990s, she sought out a highly recommended doctor who treated her with a strong dose of cruel words.

“ ‘You’re blind. What do you want me to tell you?’ ” she recalled the doctor saying. “I was so distraught by the visit; I did not go back to the doctor for years and years and years.”

About 10 years ago, though, she went to a Foundation conference, where she received a referral to a Denver retinal specialist by the name of Dr. Alan Kimura, who changed her life.

“When I finally saw Dr. Kimura, I said I don’t even know why I’m here. I walked out two hours later, and I was walking on cloud nine. It’s so important to have the right retinal doctor.”

Dr. Kimura told her she had LCA. Genetic testing gave her a confirmed genetic diagnosis of LCA10, caused by mutations in the CEP290 gene.

Linda encourages people to get genetically tested to pinpoint the diagnosis, and then, like her, to be aware of the possibility of participating in a clinical trial to advance research into treatments and cures.

People told Linda along the way that because of her blindness, she shouldn’t marry or have children or follow her passion for acting. And, of course, she heard those stinging words from that earlier doctor: “ ‘You’re blind. There’s nothing we can do.’ ”

Linda is a retired clinical social worker in geriatric long-term care, an actor in a theater company, a Foundation volunteer, a mother of four, a grandmother of seven, a motivational speaker, and the author of “Just Because I Am Blind Does Not Mean I Can’t See!”

Russ Davis

Russ Davis, 60, of Jacksonville, Fla., still gets confusing information about the cause of his rare inherited retinal disease.

“One minute I hear it’s probably LCA, or no, that it’s classic RP. I got that at the conference.”

Some retinal experts do consider LCA to be a severe form of RP.

In 2019, Russ received a genetic diagnosis of LCA2, caused by a mutation in the RPE65 gene. Dr. Stephen Russell at the University of Iowa told Russ he could have RP or LCA.

“ ‘It could be either one,’ ” he recalled the doctor saying. “ ‘But at your age with so few retinal cells, we’re not going to know.’ ”

Russ said he’s a little frustrated with the lack of a certain label for the disease, but it’s not going to change his life.

“The blindness part, that’s fine. I am who I am. It doesn’t control my life. But I’d like to have answers.”

These days, Russ is going with LCA.

His vision loss occurred at birth. Growing up he could read a book with a bright light, ride a bike, and he enjoyed long-distance running.

“I could see most everything, except at night when everything disappeared. When the sun went down, I was toast,” he said. “There was nothing there. There was darkness and light bulbs.”

His vision worsened early in his career in his mid-20s working for the State of Florida, looking for people who owed child support and wanted to stay missing. The job was fun for 30 years but about 10 years ago, with his vision getting worse and work getting harder, he retired.

Russ and his partner, Denise Valkema, were like a comedy team at the LCA session, riffing off each other’s words and making the Mix & Mingle group erupt in rounds of laughter.

Denise, who lives with optic nerve hypoplasia, which is an underdevelopment of the optic nerve, met Russ through the National Federation of the Blind. Denise served as NFB’s Florida Affiliate President for seven years.

They both serve on the organization’s board. Their priorities include working with Congress on myriad pieces of legislation to bring about better accessibility to medical care, computer technology, banking, voting, and more.

“The blind community is still not able to participate fully in society because we don’t have access to all the aspects of living that the sighted community has,” Russ said. “Try finding a talking blood pressure cuff.”

Russ advocates for people with diminishing eyesight, reassuring them that that life will go on.

“It’s all about your attitude. I try to tell them, no, that it’s not going to be easy. Lots of times, it’s going to be difficult. There are a lot of things to adjust to. You simply find new ways to do the things you were doing before.

“You can’t let your loss of eyesight define who you are or control you. You have to own it and not let it control you.”

And he lives his words.

“There’s so many times in life, you have the option to laugh or to cry, and I’m going to pick laughter. It would be very easy to pick the other one.”

Emily Townsend Cobb

With a 2½-year-old daughter, another one on the way, and a pediatric physical therapy career, we were lucky we had the chance to talk with Emily Townsend Cobb at the LCA session.

Doctors diagnosed Emily with RP at age 3. Now, 33, she received a confirmed genetic diagnosis in 2019 of LCA13, caused by a mutation in the RDH12 gene.

Emily is in that age group of people misdiagnosed for years before the advent of genetic testing.

“Thirty and over, that’s how it went,” she said.

Getting the confirmed diagnosis didn’t really change her life, especially because LCA13 research is in preliminary stages.

“Now I sit and wait for my number to be called,” Emily said, referring to the possibility of a treatment or cure for her form of LCA. “While we wait for all these things to happen, we have to live life.”

Emily’s husband, and her mom and dad accompanied her at the conference. Her father, Clay, introduced himself, saying, “Oh, I’m the proud father of two girls with RDH12 and I’d do anything to help them.”

As he broke into tears, his wife, Sue, leaned into him, saying, “He’s a crier.”

Without having to say much more, it became clear why Emily credits her family for their loving support and positive approach toward life.

She said she receives 150 percent support from her family.

“That support is so important for anybody, but especially if you have a disability.”

Doctors also diagnosed her 31-year-old sister, Ashley, with RP, and she later received a genetic diagnosis of LCA13 (RDH12).

Emily remembers reading newsprint as a pre-teen and playing soccer, but her vision profoundly worsened as a teen-ager, a tough time for any kid, but especially for her as she was losing her sight.

About the same time, she learned she had LCA but didn’t undergo genetic testing because genetic data was still being mapped out.

We talked with Emily after the session when she returned to her home in Jacksonville, Fla., where early on, she said, her mom set her up with a therapist who had RP, which helped build her confidence as a teen-ager.

She put off using a cane until college and in her sophomore year got her guide dog, a black lab named Fergie, now retired to pet life after 11 years of service.

“She’s currently snuggled up to me on the couch while I fold laundry,” Emily said as her little girl, Elora, napped.

Her second daughter is due in October. And, oh, did we mention she runs half-marathons and is a triathlete?

Emily takes part in triathlons with her husband, Ryan; they are tethered during the running and swimming races and ride a tandem bike for the cycling portion.

“If you ever want to test the strength of a marriage, blindfold one of you and tether to the other,” Emily quipped.

She and Ryan talked about the chances of their children being born with LCA. She recalled her husband saying, “ ‘Emily, if they’re going to end up as awesome as you, I want to.’ ”

They knew their children could be born with LCA, but they also knew the rarity of the disease. Emily said the chances of having a child with LCA are about one in 400.

“I’ll take those odds,” she said. “I’m pretty happy that I’m here.”

Connecticut Legislature Establishes Permanent Rare Disease Advisory Council

Connecticut Gov. Ned Lamont signed into law years-in-the-making legislation establishing a permanent Rare Disease Advisory Council (RDAC), effective July 1, 2022.

Lesley Bennett, Volunteer Ambassador for the Connecticut Rare Action Network of the National Organization for Rare Disorders (NORD), praised the bi-partisan team of the General Assembly’s Public Health Committee, Chair Rep. Jonathan Steinberg and Ranking Member Rep. William Petit, for bringing the legislation to fruition.

“This RDAC will give patients, families, caregivers, health care providers, advocates, researchers, and other stakeholders an opportunity to make formal recommendations to state agencies and our legislature on ways to develop public policy and health care legislation that will improve the lives of those impacted by a rare disease in Connecticut,” Bennett said.

Connecticut-based Hope in Focus advocated over the years with the Rare Action Network for the establishment of the council. The state created a temporary rare disease task force in 2017 that never got off the ground.

This year, in a short legislative session – with lots of input from advocacy organizations, patients, caregivers, doctors, researchers, and advisory council members from other states – Connecticut’s governor signed into law House Bill 5500, now Section 48 of Public Act 22-58, establishing a permanent RDAC.

Laura Manfre, Hope in Focus Co-Founder and Board Chair, commended the action, saying it will bring much-needed awareness to rare diseases.

“Helping people living with rare disease all begins with awareness and Connecticut’s Rare Disease Advisory Council will help with that, and more, for the 7,000 known rare diseases affecting 25-30 million people, about 10 percent of the country’s population,” she said.

“Rare disease by definition needs all the attention it can get and establishing a Rare Disease Advisory Council in Connecticut can only bring more awareness to those living with rare conditions and bring needed support to help improve people’s lives.

“Rare diseases, such as Leber congenital amaurosis (LCA) and other inherited retinal diseases (IRDs), know no geographical boundaries, so it is a terrific step for Connecticut to join the other 22 states that already have established such councils.”

Hope in Focus Gave Supporting Testimony

Hope in Focus representatives testified in the last several years at the capitol in Hartford in support of establishing a permanent council by educating legislators about our organization and LCA to demonstrate in human terms the necessity for such a council.

We told them that LCA is characterized by severe vision loss at birth, and that while some children are born with little or no vision, others may have significant vision loss in the first few years of life, stable vision for a time, and, as the retina deteriorates, eventually blindness.

We let them know that LCA patients living with one form of the rare inherited retinal disease and treated with the gene therapy LUXTURNA® experienced dramatic changes in their lives with improved or restored vision. Five, 6, 7-year-old children treated with the breakthrough drug view life in a new light in big and little ways, and they now can see rainbows arcing in the sky and stars shining at night.

The legislators also needed to know that the optimal window for reversing vision loss is during the early phase of the disease. Current clinical trials and preclinical research give hope to those with one of the 26 other gene mutations identified to cause LCA, as those scientific studies are critical to advancing treatments for LCA and other IRDs.

After the U.S. Food and Drug Administration approved LUXTURNA® in 2017, several states attempted to pass laws denying access to treatment to individuals, saying a certain degree of blindness must be met before they could access treatment. Such restrictions are unacceptable and go against federal health recommendations, which state the earlier the intervention, the better the expected outcome.

Hope in Focus made the point that no one who qualifies according to FDA guidelines should ever have to wait to be “blind enough” to receive access to treatment. We, along with other organizations, were quick to call these states out and urged the Connecticut General Assembly to support patient access to FDA-approved treatments.

Rare Disease Advisory Council Specifics

The new law establishes a 13-member Connecticut RDAC to advise and make recommendations to the Department of Public Health and other state agencies about the needs of people in the state living with a rare disease and their caregivers. Advisory councils may differ from state to state in some ways. Click here to check whether your state has an RDAC or is working to establish one.

Council members will include insurance, public health, and social services commissioners, or their designees, and 10 members appointed by the governor and the Public Health Committee leadership.

The 10 members are:

a representative of an association of hospitals or a hospital administrator, and a physician with expertise in medical genetics.
a representative of a patient advocacy group in the state representing all rare diseases, and a family member or caregiver of a pediatric patient living with a rare disease.
a representative of the biopharmaceutical industry involved in rare disease research and therapy development, and an adult living with a rare disease.
a member of the scientific community engaged in rare disease research, and a caregiver of a child or adult living with a rare disease.
a physician who treats people living with a rare disease, and a representative, family member, or caregiver of a person living with a rare disease.

Initial appointments are required to be made by Oct. 31, 2022. Under the law, five of the first-appointed members serve two-year terms; five members serve three-year terms, and all members serve two-year terms thereafter. Members are not compensated for their services but may be reimbursed for necessary expenses.

The advisory council is required to meet in-person or remotely at least six times between Nov. 30, 2022, and Oct. 31, 2023, and quarterly thereafter. The council also must provide opportunities for the public to make comments, hear council updates, and provide input on council activities.

The council also can hold public hearings to solicit comments from the public to assist with a study or a survey about people living with rare disease, their caregivers, and their health care providers.

The RDAC can consult with experts to develop policy recommendations and conduct research to make recommendations covering treatment, care, safeguards against discrimination, health insurance coverage, drug formularies, and more.

The law also requires the council, starting by Nov. 30, 2023, to annually report to the governor and the Public Health Committee on its findings and recommendations, including council activities, research findings, and legislative recommendations; and potential funding sources for its activities, including grants, donations, sponsorships, or in-kind donations.

The first meeting of the council will be by Nov. 30, 2022.

Let’s Chat About…Gene-Independent Therapies for Inherited Retinal Diseases with Dr. Daniel C. Chung

We’ve heard a lot about therapies to correct mutations in specific genes causing blindness or low vision, and now research is moving beyond single-gene correction to gene-independent therapies to help delay progression in rare inherited retinal diseases (IRDs) or to restore levels of vision.

We learned about this research from Dr. Daniel C. Chung, Chief Medical Officer of SparingVision, an ocular genomic medicine company focusing on gene-agnostic or gene-independent therapy and gene-editing approaches to combat blinding diseases.

Dr. Daniel C. Chung

Hope in Focus featured Dr. Chung in its June 21, 2022, webinar episode titled “Let’s Chat About…Gene Independent Therapies for Rare Inherited Retinal Diseases.” Courtney Coates, Director of Outreach and Development, moderated the session which can be viewed here. “Let’s Chat About…” is our free webinar series bringing together researchers, advocates, industry leaders, and people living Leber congenital amaurosis (LCA) or other IRDs for conversations important to the rare retinal disease community.

Before his recruitment to SparingVision, Dr. Chung worked with Spark Therapeutics and focused on developing LUXTURNA®. The medicine injected under the retina became the first, and so far, only, gene therapy approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in a blinding genetic disease called LCA. The drug targets IRDs due to variants in the RPE65 gene, known as LCA2 (RPE65), which is one of 27 identified forms of LCA, and helped improve vision in people who underwent the procedure that involves a subretinal injection of the medicine into each eye.

Dr. Chung served as the Ophthalmology Therapeutic Leader for Spark, where he led the medical affairs group and contributed to clinical development and operations, marketing, business development, patient advocacy, and preclinical research and development.

With more than 300 genes causing IRDs, and research underway involving myriad programs in academia and the biotech industry, Dr. Chung explained the focus of the company headquartered in Paris with offices in Philadelphia.

“What we are trying to do at SparingVision is to look at some of the ways we could do gene-independent approaches, which means we’re not necessarily correcting the genetic defect, but using other genetic parameters where we can help slow down the degeneration of disease in a gene-independent way.”

Slowing down retinal disease progression

Dr. Chung said one of the company’s preclinical research programs seeks to preserve cone function in people living with rod-cone dystrophies, concentrating on the most common form, retinitis pigmentosa (RP), which is a group of related eye disorders that cause progressive vision loss as the retina’s light-sensing cells deteriorate. The disease affects 2 million people worldwide, or about 1 in 3,500 individuals.

RP affects rod photoreceptors that provide periphery vision, along with night, dim light, and side vision, while cone photoreceptors in the middle of the eye provide the best visual acuity, color vision, and daytime vision.

The question for SparingVision Co-Founders Dr. José-Alain Sahel and Thierry Léveillard, PhD, became: Is there a connection between the death of rod and cone photoreceptors?

The team, which also included Dr. Saddek Mohand-Said, was the first to hypothesize and demonstrate that rod photoreceptors produce a protein that rescues cone photoreceptors, thereby maintaining – and prolonging – light-adapted and high-resolution vision.

They discovered what they call Rod-derived Cone Viability Factor or RDCVF, produced by the NXNL1 gene, which has two forms – a short form and a long form.

“Basically, the short form is a survival factor,” Dr. Chung said, “a factor that occurs naturally in everyone’s eyes, where these rods cells that are on the periphery secrete a protein that attaches to cone cells, and through this long mechanism of metabolic activity helps to protect the cone cells and keeps them functioning and their structure moving forward. So that’s what happens normally.

“But in diseases where you have rod cell death, you don’t have that factor being produced anymore and that’s why it’s gene independent because it really doesn’t matter why your rods are dying. It simply matters that they’re not there to produce that factor and that factor’s necessary to keep your cones functioning, to preserve vision.

“So, by using gene therapy, we’re putting that factor, RDCVF, back into the eye of patients and hopefully we’re able to slow down the degeneration of their cones, and the cones are again for your central vision, your daytime and color vision, and we hope to be able to extend that a significant period of time. As you know, most RP types have a relatively slow degeneration, so if we were able to slow that down by 40 or 50 percent, you would have significantly longer usable vision.”

The gene produces two different factors, the secreted short form and another long form that acts as a powerful antioxidant. We’ve all heard about eating your blueberries and cranberries because they are healthy and high in antioxidants, he said.

“That’s something that works within the retina as well because the retina uses more oxygen than any other organ in the body by gram weight. And because of that, there’s a lot of reactive oxygen species that are produced and so you have to dampen those, and this is what we call the long form of RDCVF.

“The long form works by being a powerful antioxidant, so that coupled with the other property of the secreted form, the two act together to help cone survival.”

Restoring Cone Cell Function

SparingVision’s second research program focuses on another factor. Preclinical research under the guidance of SparingVision Chief Scientific Officer Dr. Deniz Dalkara deals with restoring function to cone cells that have lost the ability to function, but their cell body remains.

These dormant cones are viable cones with diminished outer segments that no longer respond to light, as such that the patients’ light response decreases, and they become unable to see. Since the phototransduction cascade – the process through which photons, or elementary particles of light, are converted into electrical signals, which allows for normal vision – occurs in the outer segment of the cones, these dormant cones are no longer capable of converting light into an electric signal, leaving patients with decreased vision and, as the disease progresses, blindness.

SparingVision research involves an injection that provides dormant cone cell bodies with a channel protein that would allow to restore a short phototransduction cascade within the dormant cone, restoring electric signals, and thereby possibly restoring light sensitivity, visual acuity, and color vision.

“This we believe will actually restore function to cone cells that have lost the ability to function, but their cell body remains. In retinal degeneration, we see that the function is lost, and certain types of structure is lost, but the main cell body stays intact,” he said.

“You can revive those dormant cone cells and thereby restore some level of vision. Again, it doesn’t matter why they degenerated, so it’s not gene dependent because we’re not correcting the gene that caused the degeneration, but we’re adding another factor in that.

Dr. Chung said human trials will start “we hope, very soon.”

He also described the company’s CRISPR gene-editing research, in which the therapy acts as molecular scissors, cutting or editing out gene misspellings that cause dysfunction.

Regarding the company’s research projects, Dr. Chung said, “We’ve gone from one end, where we are gene independent and then we’ve gone all the way to the other side, where CRISPR is not only gene dependent, but it’s also dependent on the misspelling within that gene, and each gene has a lot of misspellings that can cause disease, and so this is a little more targeted.”

Genetic Testing Still Necessary

Dr. Chung said it is still critical that people get a confirmed genetic diagnosis through genetic testing, accompanied by genetic counseling.

“Even though we may be gene independent, I think that the idea is we still want to encourage people to get their genetic diagnosis.”

A definitive diagnosis will help people understand their retinal disease, learn about rates of disease progression, and get connected with patient community organizations, such as Hope in Focus, he said.

On SparingVision, Dr. Chung said the business is not just a gene therapy company.

“We totally think of ourselves as a genomic medicine company, and that’s really using all the genetic tools that are in the toolbox to combat these inherited retinal diseases or ocular diseases in general.”

The company wants to work on many different approaches to have more choices for a tailored therapeutic option.

“We just want to do as many different strategies as we can to try and get more options for patients. I think obviously it would be great to be in a world where it’s not a matter of having one therapeutic option but to have several therapeutic options that are tailored toward where you are in your disease progression and what fits best for you and the inherited retinal disease or ocular disease that you have.”

Let’s Chat About…Advancing Treatments into Clinical Trials with Ben Shaberman

Innovative funding initiatives created by the Foundation Fighting Blindness are accelerating research advances to find treatments for Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs).

Preclinical research involving animal models often gets stuck in early phases because no funding exists to move into clinical trials where developing treatments can be evaluated on people and advanced toward regulatory approval.

“The science is there; it’s the money that’s needed to fund the clinical trials, especially in later stages,” according to Ben Shaberman, the Foundation’s Senior Director of Scientific Outreach and Community Engagement.

Ben Shaberman

He appeared in a recent webinar episode of our Let’s Chat About online series, in which he detailed strategies driving retinal disease research.

Courtney Coates, our Director of Outreach and Development, moderated the episode, “Let’s Chat About… Advancing Treatments into Clinical Trials: Opportunities and Challenges,” featuring Shaberman, who has been with the Foundation about 17 years. You can view the session here.

Shaberman writes for the Foundation’s electronic and print publications, presents the latest scientific retinal research advancements at local and national events for patients and families, and conducts science training activities for staff and constituents.

He launched a podcast series last year called “Eye on the Cure” and enjoys collaborating with people one-on-one to help them understand their retinal disease and the research underway that could benefit them.

He also leads the company’s outreach to eye care professionals throughout the United States to help educate their patients about resources available to patients with low vision or blindness.

Shaberman earned a Master of Arts degree in writing from Johns Hopkins University, a Master of Science degree in systems management from the University of Maryland, and a Bachelor of Science degree in computer information science from Cleveland State University.

The Foundation is the world’s leading private funder of research on potential treatments and cures for inherited retinal degenerative diseases, including age-related macular degeneration. The nonprofit has raised more than $850 million to find cures for retinal diseases, identify more than 300 genes linked to them, and launch more than 40 clinical trials for potential treatments.

Foundation Funding Programs

Preclinical research or laboratory research done in academic research centers globally is expensive.

“But, when you are moving those emerging therapies from the labs, the cost goes up dramatically and that’s a big barrier for researchers,” Shaberman said. “It costs millions of dollars just to get in that clinical stage.”

That stage brings humans into the research, pulls in the U.S. Food and Drug Administration as a regulator and overseer, and requires submitting to the FDA required applications explaining the research and demonstrating the developing treatment’s safety and efficacy.

“That’s a really intensive process,” he said. “They (these early-stage therapies) may never see the light of day in a clinical trial because of all these issues.”

The Foundation created two programs to help drive projects to clinical stages.

The first, its Translational Research Acceleration Program (TRAP), helps scientists refine preclinical studies and accelerate research toward clinical trials to provide a robust pipeline of potential therapies to fight IRDs.

“TRAP helps researchers do some of that later stage work that will hopefully help them get to the clinical-trial doorstep,” Shaberman explained.

TRAP is funding a study at the Casey Eye Institute focusing on neuro-protective treatments to help reduce inflammation and other symptoms common to retinal diseases. Funding also supports Usher Syndrome Type 3a later-stage lab work.

The second program is the Foundation’s Retinal Degeneration Fund (RD Fund) and marks a step forward from TRAP because it invests in start-up companies. Like a venture capitalist, the investment is looking for a return, which instead of going into investors’ pockets, goes to the RD Fund to help projects in or advancing toward early-stage clinical trials.

“The ultimate goal is once you move something into a clinical trial and help those companies do that, if you can get some early encouraging signals, you can attract tens or hundreds of millions to fund that process.”

The RD Fund led the $19 million in seed financing to create Opus Genetics, the first spin-out company internally conceived and launched by the Fund to further the Foundation’s mission.

The new gene therapy company plans to target two forms of LCA: LCA13 (RDH12), which affects one in 288,000 people, and LCA5, which encodes the lebercilin protein and affects about one in 1.7 million people.

The RD Fund also helped advance ocular gene therapy research by Shannon Boye, PhD, and Sanford Boye, founders of Atsena Therapeutics.

BioBonds Congressional Legislation

Another initiative supported by the RD Fund, Hope in Focus, and two dozen more groups is a proposed Congressional Act designed to help researchers launch clinical trials for emerging treatments and gives hope for getting more treatments across the finish line for people living with a broad range of medical conditions, including rare retinal diseases.

This BioBonds legislation establishes loans up to $25 million to a researcher or company as an innovative way to finance early-stage clinical trials. The program would provide $10 billion annually for three years, and researchers would be required to repay the low-interest, government-backed loans.

Shaberman encouraged his webinar audience to go to the BioBonds website for more information and email him about supporting the proposal.

He said he has always been inspired by the courage of patients and families and their success in coping with challenging conditions. They often motivate friends to help with fundraising and get more people involved with advancing research. The stories coming out of the Foundation and Hope in Focus create connections between families and foster positivity and success.

He cited Hope in Focus for its support of the Foundation’s free genetic testing program to get a confirmed genetic diagnosis, a vital step in the journey toward understanding a person’s specific retinal disease caused by a gene mutation.

Fifteen years ago, a handful of trials were underway. Researchers now are working on more than 40 clinical trials.

“A lot has happened. It can never happen quickly enough, but we’re doing everything we can to accelerate the science, and, in the end, science takes time.”

ProQR Announces Updates and Priorities After Illuminate Trial Analyses

ProQR Therapeutics completed an in-depth strategic review to prioritize its objectives toward advancing RNA therapies, following news that its Illuminate Phase 2/3 clinical trial of sepofarsen in LCA10 CEP290 did not meets its primary endpoint of improving visual acuity.

The Dutch-based biotechnology company delivered an update on its sepofarsen program after a comprehensive analysis of data from the Illuminate trial and it announced a corporate restructure and workforce reduction.

Based on information from the review, ProQR will prioritize two strategic objectives dealing with genetic eye disease and RNA editing technology.

The company plans to explore a development path for selected genetic eye disease programs subject to regulatory feedback from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).

Regarding RNA editing technology, ProQR will accelerate development of the Axiomer® RNA editing technology platform and pipeline activities expanding into areas beyond the eye, including initially the liver and central nervous system. The technology aims to correct disease-causing genetic mutations and reverse the underlying course of currently untreatable diseases.

Daniel A. de Boer, Founder and CEO of ProQR Therapeutics, said in a statement: “We are focusing our strategy on accelerating our Axiomer® RNA-base editing platform technology and a select pipeline of RNA therapies for inherited retinal diseases (IRDs) as we remain committed to developing RNA therapies for patients with high unmet need.”

Corporate Reconstruction and Priorities

ProQR also plans to reduce expenses by making program priorities, changing its corporate structure, and reducing its workforce by a third.

The company will focus its ultevursen QR-421a program for USH2A-mediated Usher syndrome and retinitis pigmentosa (RP) on a single Phase 2/3 Sirius trial, with the potential of an interim/futility analysis next year.

ProQR is suspending all other research for IRDs, including its QR-1123 program for autosomal dominant RP and its QR-504a program for Fuchs endothelial corneal dystrophy.

The business also will reduce its workforce by about 30 percent, including the departure of its Chief Scientific Officer Naveed Shams, MD, PhD.

Co-Founder and Supervisory Board Chair Dinko Valerio said in a statement:

“We believe deeply in the promise of RNA therapies, the Company’s pioneering efforts in this field, and ProQR employees. These are the right steps to take to offer the best opportunity to create long-term value for all of our stakeholders, including our shareholders whom we thank for their support, and the communities we aim to serve.”

De Boer thanked the people leaving the company for their significant contributions toward the company’s mission. He characterized the changes as extremely difficult decisions necessary to drive long-term growth and value.

“I also want to acknowledge the disappointment that many in the eye disease community may feel today, particularly individuals and families living with autosomal dominant retinitis pigmentosa and Fuchs endothelial corneal dystrophy as we wind down our programs for these indications.”

Sepofarsen Update

Following the top-line data announcement in February that Illuminate, ProQR’s pivotal Phase 2/3 trial of sepofarsen in LCA10, did not meet the primary endpoint of Best Corrected Visual Acuity (BCVA) at month 12, compared to a sham procedure control group, comprehensive analyses revealed no technical errors in the trial conduct, data handling, or the medicine product used.

The overall safety profile of sepofarsen was consistent with earlier trials. When the effect in the sepofarsen treated eye was compared to the untreated eye in the same patient, at month 12, a benefit in vision was observed. This effect was not observed in the control group that received a sham treatment.

Overall, the post-hoc analyses showed that the efficacy seen with sepofarsen when comparing the active treatment and sham eyes to their corresponding untreated contralateral eyes across BCVA, Full Field Stimulus Test (FST), and other endpoints is more consistent with the results seen in earlier trials, where the untreated contralateral eye was used as the control.

Based on these results, ProQR will focus on core activities related to sepofarsen. The company plans to meet with the EMA and FDA to discuss these data from the Illuminate trial and share an update later this year.

ProQR currently plans to continue Illuminate, which is a two-year study, the Brighten pediatric study, and the Insight open-label extension study, until further regulatory guidance.

Aniz Girach, MD, Chief Medical Officer of ProQR Therapeutics, said in a statement:

“While we were disappointed by the outcome of the primary analysis, we believe that these post-hoc analyses and the observation that approximately a third of the patients benefited across multiple concordant endpoints in this trial, in combination with the high unmet need in LCA10, warrants a discussion with the regulators.”

Data from the Illuminate trial will be presented at the annual Retinal Cell and Gene Therapy Innovation Summit on April 29, 2022, and at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting from May 1-4, 2022.

Let’s Chat About … Opus Genetics with Ben Yerxa

Working with preclinical data from multiple Leber congenital amaurosis (LCA) studies at the same time, Opus Genetics hopes to advance research into gene therapy for several forms of LCA at a faster pace.

Ben Yerxa, PhD, and acting Chief Executive Officer of Opus, told a Hope in Focus webinar audience that good preclinical data from Opus Co-Founders Jean Bennett, MD, and Eric Pierce, MD, became the foundation for the company’s first two projects researching LCA5 (Lebercilin) and LCA13 (RDH12).

Yerxa, who also is CEO of the Foundation Fighting Blindness and its Retinal Degeneration Fund (RD fund), explained that while Dr. Bennett researched what came to be the LCA2 (RPE65) gene therapy LUXTURNA®, other projects awaited advancement to preclinical stages. Dr. Pierce’s preclinical work also became part of Opus’ advancing work.

Ben Yerxa

Yerxa discussed biotechnology company’s aspirations as part of the Hope in Focus “Let’s Chat About …” webinar series. Our March episode, moderated by Courtney Coates, Director of Outreach and Development featured Yerxa, acting CEO of Opus based in Raleigh, N.C. Click here to view the webinar.

The Foundation’s RD Fund led the $19 million in seed financing for the company founded last fall, with participation from the Manning Family Foundation and Bio Partners.

The Magic of a One-of-a-Kind Model

Opus is the first spin-out company internally conceived and launched by the RD Fund to further the Foundation’s mission. The RD Fund is investing in projects that are in, or advancing toward, early-stage clinical trials.

“Opus is a first-of-its-kind model for patient-focused therapeutic development,” Yerxa said. “As the first company launched by the Foundation’s venture arm, RD Fund, Opus is uniquely positioned to bring experts, resources, and patients together to efficiently advance ocular gene therapies for small groups of patients that to date have been neglected.”

The company decided to take on the development of multiple gene therapies, regardless of the small treatment population for rare retinal diseases.

“Opus was really born out of necessity,” Yerxa said. “Many gene therapies in preclinical development were just not being developed further.”

The company would even work on programs where only 100 patients have a particular retinal disease, or where the patient population is smaller or larger than the 1,000 to 2,000 people in the United States with LCA2 RPE65, a form of LCA treated with LUXTURNA®. The gene therapy, developed by Spark Therapeutics, is the only federally approved treatment for an inherited gene mutation.

“It evens out as a blend,” he said. “That’s kind of where the magic is.”

The biotech’s lead program, OPGx-001, addresses mutations in the LCA5 gene that encodes the lebercilin protein. LCA5 is one of the most severe forms of LCA and affects about one in 1.7 million people in the United States.

Its second program, OPGx-002, focuses on restoring protein expression and halting functional deterioration in people with retinal dystrophy caused by mutations in the retinal dehydrogenase gene, knowns as RDH12 or LCA13. The disease affects one in 288,000 people in the U.S.

Its third program, OPGx-003, targets LCA9 caused by NMNAT1 mutations and affects about one in 432,000 people in the U.S.

Yerxa said Opus is hoping to raise $70 million or more in the next six to nine months to bring it through 2024-25.

He advised people interested in the research to keep in communication with their physicians because as clinical trials get ready to begin, Opus will be looking for individuals to take part in them.

LCA5 Clinical Trials Planned Later This Year

Opus is looking at filing for an Investigational New Drug (IND) application with the U.S. Food and Drug Administration by the middle of this year before enrolling people for clinical trials by summers’ end at the University of Pennsylvania for LCA5. By filing for an IND, a company is asking for permission to start human clinical trials and to ship an experimental drug across state lines before approving a marketing application for the drug.

“We’re looking forward to getting that started so we’ll be a clinical-stage company.”

Their work also will center on what Yerxa called a tried-and-true approach to delivering the medicine through Adeno-associated virus (AVV) vectors, the leading platform for gene delivery for the treatment of a variety of human diseases.

In today’s world of retinal gene therapy development, AVVs are most often used to deliver therapeutic genes to cells in the retina, according to the Foundation. Gene therapy is administered by injecting a tiny drop of liquid underneath or near the retina. AAVs are safe and able to penetrate cells with their genetic cargo. They naturally occur in humans and don’t cause any known illness. For regulators like the FDA, that excellent safety profile is highly desirable.

Having available multiple inventories for developing therapies and working with the university to license the technology can speed up the pace of research and manufacturing, reducing the average two-year timeline for clinical work.

“I think we can shave off many months of the timeline,” Yerxa said.

In the question-and-answer session following the webinar, one viewer asked about taking on research into a form of LCA caused by a mutation in the IQCB1 gene, and Yerxa replied, “We are aware of that work and interested in this asset.”

He suggested people keep connected with Opus and receive company emails for updates on projects. https://opusgtx.com/contact/

Let’s Chat About … Self-Advocacy and Supporting Your Child’s Education with Beth Borysewicz

Children living with visual impairment become more independent and empowered when parents set high expectations for their kids and challenge them every day.

Just ask Beth Borysewicz. In her role with Connecticut’s Bureau of Education Services for the Blind, she makes a living helping children with visual disabilities realize their potential as strong, self-determined adults. And she’s the first one to say, often with tears in her eyes, that her job is to work herself out of a job.

Beth Borysewicz

She described her work in helping children from birth to 22 years old with visual impairment or blindness become more independent as adults as part of the Hope in Focus “Let’s Chat About …” webinar series. Our March episode, moderated by Courtney Coates, Director of Outreach and Development, featured Borysewicz, an Education Consultant for the Department of Aging and Disabilities, Bureau of Education Services for the Blind.

We developed the series with those living with Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs) in mind, but we invite all members of our community, including those in research, industry, and the regulatory communities to join any of the sessions, as we look ahead to a common goal of advancing treatments for rare retinal disease. Click here to view this episode.

Borysewicz found her passion working with the blind and low-vision community unexpectedly 16 years ago, when she had a 3-year-old student named Sofia, who was diagnosed with LCA. Yes, that would be the same Sofia as in Sofia Sees Hope, our organization’s original name until a recent rebranding to Hope in Focus. Borysewicz also is Vice Chair of our Board of Directors.

She said parents need to be the biggest advocates for their children.

“If you think your child is not getting what they need, you can ask for it.”

She also encouraged connections with people who have been on this journey before, bringing to mind the Hope in Focus Family Connections program that helps ease feelings of isolation that can arise when a family member is diagnosed with a rare disease.

“It’s the people that have already gone through it who will help you the most, including Hope in Focus. That’s why I’m on the board. What Hope in Focus does for families is immeasurable.”

All the Little Things We Do Every Day

As a Teacher of Students with Visual Impairments (TVI), Borysewicz focuses on teaching students self-advocacy and exploring the Expanded Core Curriculum (E.C.C.), distinguished from a school’s standard core curriculum consisting of courses in math, science, reading, and the like.

E.C.C. comes from the perspective of teaching students with blindness or low-vision and encompasses nine areas: Compensatory Skills, Orientation and Mobility, Social Interaction, Independent Living, Recreation and Leisure, Sensory Efficiency, Assistive Technology, Career Education, and Self-Determination.

The curriculum is more than a checklist or lesson plans for learners with a visual impairment, according to The E.C.C. and Me website. It’s all the little things we do every day, done with intention so children with visual impairments can learn skills they need for a fulfilling life.

“I wish everyone would do what I do,” Borysewicz told her webinar audience. “There is a shortage worldwide of TVIs.”

She advised parents to set expectations high for their children, challenge them every day, and give them a safe place to learn.

“Children can do anything they set their minds to. Do anything you can do to empower them,” she said. “Celebrate everything. Celebrate every little thing.”

She talked about self-determination, saying it’s her favorite part of the curriculum and the most important.

“It’s teaching a child to believe in themselves and just take that leap,” she said. “It’s taking that step off the curb to cross the street with a cane or initiating a conversation at a lunch table that builds self-confidence.”

Making Learning Fun and Exciting

Her work with people from birth to age 22 encompasses figuring out resources for newly diagnosed children, for school-aged students, and for young adults transitioning to the workforce or college.

“I switch hats from appointment to appointment every day,” she said. “As you can tell, I love my job.”

Working with individualized education plans (IEP), she and her team helps students become the best they can be in all the E.C.C. areas.

“It’s so important for the student to say, ‘This is what I need and why I need it,’ and just building those skills will make them successful as adults.”

And a lot of it is fun, especially with Borysewicz who excels in the Recreation and Leisure department. It goes back to when she was growing up and her dad always told her she was good at playing with people and should get a degree in play.

She implements that play degree often by creating board games to make math more fun or putting together programs to help students from prekindergarten through grade 3 explore the nine E.C.C. areas in their daily lives.

In an Expedition to Explore, students in the Young Passport Program worked on accumulating life skills at home over the summer. Each student has a passport consisting of pages designated for each of the nine E.C.C. areas, with a slant toward adventure. For example, “Career Education Caves” focuses on conversational skills, encouraging children to stay connected with their friends over the summer, known in the business world as networking, and holding mock interviews with their siblings or stuffed animals.

In “Self-Determination Safari,” a goal is to get the child to ask for help. A parent asks a child to do an unfamiliar chore, such as taking out the trash or putting toys away but doesn’t give guidance on how to do it or where to put the trash or toys, prompting or encouraging the child to ask for assistance or directions.

“Social Skills Glaciers” encourages children to spread kindness to neighbors and the community and recommends an online guide called “100 Acts of K i ndness for Kids.” Activities include listening, following directions, taking turns, ignoring distractions, cooperating, and showing empathy. (Sounds great for adults, too!)

Resources for People with Blindness or Low Vision

Borysewicz talked about her work from the perspective of Connecticut and said services may differ from state to state.

She authors a blog dedicated to professionals, families, and students called I Love Brl (Braille) and she provided webinar viewers this list of resources:

9 More than Core; The Independent Little Bee; Expanded Core Curriculum Ideas for Preschoolers and Early Elementary; Is My Child Getting a Quality V1 Program?; Integrating E.C.C. Activities into Literacy Instruction; Family Connect; and Wonder Baby.

Mother of Toddler Living with LCA6 RPGRIP1 Collaborates with Biotech Odylia to Help Advance Gene Therapy Research

After crazy months of looking for answers to questions about her infant’s vision, Melissa Matias learned her baby girl, Dylan, had a form of Leber congenital amaurosis known as LCA6 caused by mutations in her RPGRIP1 gene, a protein needed for healthy photoreceptors.

“I put my big-girl pants on and said, ‘This is the card she and I have been handed.’ ” The Georgetown, Texas, mom added: “There’s a reason for this.”

When Dylan received her confirmed genetic diagnosis in May 2020 at age 5 months, her mother did not assume someone else had the time or resources to search for a treatment or cure for her daughter’s form of blindness. Melissa organized people, advocates, and information. She created the RPGRIP1.com website and began collaborating with the nonprofit biotech Odylia Therapeutics on a $4 million fundraising effort to advance therapy for the RPGRIP1 LCA6 program.

The Atlanta-based biotechnology company is in late-stage preclinical trials, with the goal to be in clinical trials in about two years. Melissa is hoping Dylan – a gregarious trampoline-jumping gymnast – will benefit from this developing gene therapy.

Dylan in a pink stripped shirt and sunglasses, bouncing on her trampoline — Dylan on her trampoline

“We aren’t trying to fix or change Dylan. There’s nothing wrong with her. But if there’s a chance for gene therapy to enhance her life, you would want to do that,” she said. “Blindness doesn’t mean darkness. It means ‘I can do this; I just might need to do it in a different way.’ ”

Dylan’s doctor told the Matias family that the possibility of sight-saving therapy coming to fruition was not a matter of if, but when.

“This therapy, if it’s in reach, let’s get going,” Melissa said. “Let’s get the word out and open the door to gene therapy, not just for RPGRIP1, but for other genetic visual impairments and rare diseases.”

Financing poses the major obstacle. Melissa enlisted the help of patient families and organizations, such as Hope in Focus, to help spread the word and secure necessary funding to bring the treatment to market. About $115,000 has been raised, including donations from Dylan’s brothers, 8-year-old Colton and 12-year-old Brayden.

Funded by Massachusetts Eye and Ear and the Usher 2020 Foundation, Odylia Therapeutics started in 2017 with the goal of facilitating treatments for low-prevalence retinal disease with proof-of-concept science to Phase I/II/III clinical trials.

LCA6/RPGRIP1 Gene Therapy – Following LUXTURNA® Path

The gene therapy uses vector technology developed by Odylia Co-founder Luk Vandenberghe, PhD, Director of the Grousbeck Gene Therapy Center at Mass Eye and Ear, and Assistant Professor of Ophthalmology at Harvard Medical School. The research builds on proof-of-concept data generated at Mass Eye in the labs of Vandenberghe and Eric Pierce, MD, PhD, a physician and surgeon at Mass Eye and the William F. Chatlos Professor of Ophthalmology at Harvard Medical School.

LUXTURNA® currently is the only gene therapy on the market. Developed by Spark Therapeutics and federally approved in 2017, the drug treats a form of LCA known as LCA2 (RPE65), and it is the only gene therapy approved in the United States for any inherited disease.

Odylia hopes to follow in LUXTURNA’s path with its research. Delivered by injection under the retina in each eye, LUXTURNA® has helped improve vision in patients for the last four years.

“The success of LUXTURNA has proven to be life changing for many patients,” Odylia said in a news release. “It’s very exciting that with the efforts of Odylia, those affected with RPGRIP1 mutation could possibly have the same opportunity in the near future.”

Developing treatments and administering them to young patients is paramount to stall vision deterioration, as LCA6, along with the more than 27 forms of LCA, is degenerative.

Odylia says its goal is to bring proven therapeutics to patients, regardless of the number of people with the disease or the opportunity for a company to make money.

By identifying promising treatments, the company said it can partner with patient groups, community experts, and financial sponsors to develop strategic, scientific, and clinical plans. Through collaboration with industry and foundations, the organization said it can move treatments from concept through development and to patients with rare diseases.

These partnerships are needed for the estimated $3.9 to $4.3 million in development costs to advance the research through toxicology studies and fund clinical manufacturing costs. Odylia says it will work to lower costs and reduce overall expenses.

Partnerships and funding also will help with Odylia submitting an Investigative New Drug (IND) application to the U.S. Food and Drug Administration. Federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. Because a sponsor will probably want to ship the investigational drug to clinical investigators in many states, it must seek an exemption from that legal requirement. The IND is the means through which the sponsor technically obtains this exemption from the FDA.

Mom (L) with Dylan and Dad (R) sitting on a brown couch — Dylan with mom (Melissa) and dad (James)

LCA6/RPGRIP1 Research Receives FDA Designations

The FDA recently granted both orphan drug and rare pediatric disease designations for Odylia’s lead gene therapy. The company said the designations are granted for the “treatment of RPGRIP1 mutation-associated retinal dystrophies,” which most commonly includes LCA6 but is also associated with diagnoses of cone-rod dystrophy 13 (CORD13) and forms of early-onset retinitis pigmentosa (RP).

“Receiving orphan drug and rare pediatric disease designations represents an important milestone for Odylia and recognizes the potential of this gene therapy to deliver life-changing results to LCA6 patients and RPGRIP1 associated retinal dystrophies,” according to Ashley Winslow, PhD, Odylia’s Chief Scientific Officer.

Between 400 and 600 people are affected with LCA6 in the U.S., with about 20,000 globally.

Orphan drug designation is granted to therapeutics intended for treatment, diagnosis, or prevention of diseases affecting fewer than 200,000 people in the United States. Rare pediatric disease designation is granted to serious or life-threatening rare diseases that primarily affect individuals under age 18. Orphan drug and rare pediatric designations provide companies like Odylia with benefits, including access to research grants to support clinical studies, waiver of regulatory fees, seven-year marketing exclusivity, and eligibility for a priority review voucher.

Dylan with a Hula hoop at the gym — At the gym

Struggle to Find Confirmed RPGRIP1 Diagnosis

Melissa’s persistence pushed her through incredibly trying times, having six back-to-back miscarriages during 2016 and 2017 after having her two sons. Two years later, she and her husband, James, got the news she was pregnant with Dylan.

“She was so meant to be,” Melissa said. “It was unreal when it came time to deliver. Everyone in that room was crying.

“They had all seen on my chart that I had 10 pregnancies. They were all just like…” she said trailing off. “It was such an emotional time.”

Two months later, though, Melissa and James realized something didn’t seem right with Dylan’s vision; her eyes jerked from side to side from a condition known as nystagmus. It was February 2020 with the tentacles of COVID spreading over the globe, creating an overworked, overwhelmed medical world focusing on patients infected with this strange new virus.

Finding an initial diagnosis for Dylan proved extremely difficult, especially when one doctor said nothing was wrong, probably just delayed maturation of vision, and another mentioned LCA but brushed it off. So, Melissa did what we all do now when we don’t get answers: She Googled the disease.

“The more I learned about LCA, I knew in my heart right away what we were looking at. But I’d also think, it’s so rare, what are the chances?”

She also learned the next step to move forward with treatment or care for 2-month-old Dylan depended on a confirmed genetic diagnosis determined through genetic testing.

No genetic testing, not now, she was told. Not until COVID is over. Melissa wasn’t waiting for the end of the pandemic, now into its third year. She knew she needed a doctor’s order but hadn’t yet connected with a retinal specialist; she sought out the help of Dylan’s pediatrician, a doctor she characterized as amazing, who ordered the test.

Waiting for the results, Dylan’s parents scheduled an appointment for May 28with a Houston retinal specialist; the confirmed diagnosis of LCA6/RPGRIP1 came through May 27, paving the way to finding resources in orientation, mobility, and education for Dylan.

Living with LCA6/RPGRIP1 / Like Mother, Like Daughter: Stubborn and Persistent

Dylan is now 2 years old. Her parents believe she has tunnel vision and does best seeing objects 10 or 15 feet away. She’s better now at keeping her glasses on, rather than ripping them off all the time like she used to.

On her first day of Orientation and Mobility training, she picked up a cane and used it just the right way, a milestone the instructor said he had never seen in a child her age.

“Indoors, she’s just amazing,” Melissa said. “She loves picture flashcards, playing in her toy kitchen, always wants someone to read her books, and she loves her new mini trampoline she got for Christmas. And music – she loves to sing and dance.”

Dylan takes her time in new environments and is a little more cautious than other toddlers because of her visual limitations. With photophobia being one of the symptoms of LCA, Melissa said her daughter finds bright outdoor sunlight to be the most challenging and where she relies more on her cane skills.

The little girl also is very vocal and visual.

“Her vocabulary is comparable to a child much older than 2,” Dylan’s mom said. “We know she is very visual, something we feel blessed with, since LCA can present with a wide range of visual capabilities. We’ve actually had to teach her to bend down and feel for objects she drops, because her instinct is always to look for something first.”

She’s also persistent.

“She has a very strong desire for mastery, having to do things over and over again. She likes a challenge.

“I have no doubt this girl is going to change the world. No matter what happens if gene therapy comes about for her or not. She’s going to be on skis this winter. I’m not going to give her an excuse not to do something or at least to not try.

“She can and will do anything she wants, just in her own ways. Stubborn and persistent, exactly what she needs.”

Dylan standing in between her brothers with skis on. — With her brothers, Colton and Brayden

LCA10 CEP290 Illuminate Clinical Trial Produces No Observed Benefit

ProQR Therapeutics’ clinical trials of sepofarsen to treat a form of Leber congenital amaurosis (LCA) caused by a mutation in the CEP290 gene did not meet its primary endpoint of improving visual acuity.

Illuminate, the name of the clinical study, aimed to explore whether the investigational medicine sepofarsen was effective and safe for people with LCA10 caused by the CEP290 mutation.

The Phase 2/3 clinical trial produced no observed benefit in visual acuity for participants receiving the treatment versus those in the study not receiving the treatment. Visual acuity is a measure of the ability of the eye to distinguish shapes and details of objects at a given distance.

ProQR Founder and Chief Executive Officer Daniel A. de Boer delivered the news recently and characterized the results as disappointing.

“Given the results observed in earlier studies of sepofarsen, the Illuminate trial results are unexpected and disappointing, especially for people living with LCA10,” de Boer said.

“ProQR was founded with the goal of developing RNA therapies (ribonucleic acid) for patients with high unmet medical need, and we will continue to advance our robust pipeline of therapies for genetic eye disease. We are deeply grateful to all of the participants, their supporters, and investigators who participated in the Illuminate study.

“Since the results in February, ProQR has been conducting additional analyses of Illuminate and will present these findings at a future scientific conference.”

ProQR works on developing RNA therapies to treat LCA and other inherited rare diseases (IRDs). With DNA being the library of our genes and RNA being a blueprint of that collection, RNA therapies help carry out DNA instructions to create certain proteins critical to a healthy cell.

Analyzing Results for More Answers

Hope in Focus Co-Founder and Board Chair Laura Manfre said we will share updates with the LCA community as we learn more from ProQR.

“The results are not what we had hoped for from ProQR on the LCA10 Phase 2/3 trial, but we are resolved to keep hope in focus, knowing that the brilliant minds that got us this far are not giving up.

“It’s important to remember when there are setbacks that only 10 years ago, all we had was hope. Most of the community couldn’t even get a genetic diagnosis, let alone hope for treatment,” she said. “We’ve come a long way in a short period of time, and we’re going to keep advancing.”

Ben Yerxa, PhD, Chief Executive Officer of the Foundation Fighting Blindness, said his organization will work with ProQR to learn more about the data.

“This was not the outcome we had hoped for, and we share in the disappointment many are feeling in the community,” Yerxa said.

“We will continue to work alongside ProQR to learn more from the ongoing analyses and as they work to advance RNA therapies to potentially help children, adults, and families who are affected by rare genetic eye diseases.”

In delivering the results, the biotechnology company gave background about LCA, the most common genetic cause of childhood blindness, affecting about 15,000 people in the Western world. One federally approved gene therapy treatment, LUXTURNA®, exists for people with LCA2 (RPE65), one of the more than 27 forms of LCA.

The rare retinal disease usually appears in the first year of life and is characterized by progressive loss of vision. Other symptoms can include rapid eye movement, known as nystagmus, eye-poking, night blindness, and sensitivity to light, known as photophobia. Depending on the mutation, complete loss of vision can occur during early childhood.

**Specifics of the LCA10 CEP290 Trial**

Illuminate enrolled 36 participants, aged 8 years or older with genetically confirmed LCA10 due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290 gene.

The study was a randomized, sham-controlled clinical trial that took place in three randomized groups at 14 sites in nine countries.

The first group received a target dose of sepofarsen by intravitreal injection (IVT), the second received a low dose via IVT, and the third underwent a sham procedure that mimicked an injection with no medicine or injection given.

Bart P. Leroy, MD, PhD, one of the study’s key investigators and Director of the Ophthalmic Genetics and Retinal Degenerations clinics in the Division of Ophthalmology and Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia (CHOP), said work will continue toward finding therapies.

“LCA10 is devastating, and with no approved therapies, very difficult to treat retinal disease resulting in blindness,” said Dr. Leroy, who also is head of the Ophthalmology Department at Ghent University Hospital and Professor of Ophthalmology and Ophthalmic Genetics at Ghent University in Belgium.

“We will continue to work with ProQR to understand the data as they work for advance therapies for individuals with inherited retinal diseases.”

Andy Bolan, ProQR Director of Medical Affairs, said the team extends its thanks to the study participants, their supporters, the investigators, and their staff for support in developing the trial. He said the biotech remains committed to making a significant and positive impact on the lives of those affected by genetic conditions.

For quarterly news and future study participation opportunities, you can sign up for the ProQR Eye Connect Newsletter or follow them on social media.

People also can contact ProQR with any questions at patientinfo@proqr.com.

Rare Disease Day 2022: Hope in Focus Promotes Rare Disease Advisory Council

Rare Disease Day 2022 kicked off today as people gathered across the country, including us here at Hope in Focus, to raise awareness and generate research for treatments and cures for rare diseases, including Leber congenital amaurosis and other rare inherited retinal diseases.

Hope in Focus joined more than 30 advocates gathered for a virtual celebration of Connecticut’s Rare Disease Day. The day, officially acknowledged annually on the last day of February, is celebrated nationally and globally as a concerted effort to raise awareness, to grant access to medications, therapies, and state services, and to encourage research on the more than 7,000 rare diseases.

The Rare Action Network (RAN) of the National Organization for Rare Disorders (NORD) organized Connecticut’s Rare Disease Day activities, the highlight of which was to inform the state legislature of the vital importance of establishing a Connecticut Rare Disease Advisory Committee (RDAC).

Courtney Assad, Hope in Focus Director of Outreach and Development, presented a statement from our organization in support of and RDAC, telling the group that research and investment paid off immeasurably with the development by Spark Therapeutics of LUXTURNA®.

“LCA patients treated with LUXTURNA® experienced dramatic changes in their lives with greatly improved or restored vision,” she said in the statement. “Five, 6, 7-year-old children treated with LUXTURNA® view life in a new light in big and little ways. They can now see rainbows arcing in the sky and stars shining at night.”

One in 33,000 people are affected by LCA, which represents 5 percent of all retinal dystrophies.

More than 20 states have established such councils and RAN is working toward creating a group for each state. This year, Connecticut’s attempt to establish an RDAC has move farther along than any of the efforts that began in 2015. A task force met a dozen times between 2017 and 2019, but a paper reporting the group’s recommendations never made it to the Public Health Committee of the Connecticut General Assembly.

RAN and NORD drafted legislation referred to as House Bill 5260 and called “An Act Establishing a Rare Disease Council.” We received great news that that the legislation was formally introduced and has been referred to the Joint Committee on Public Health. A public hearing is expected to be scheduled to hear testimony supporting the proposed legislation.

The council would advise and make recommendations to the Department of Public Health and other state agencies, regarding the needs of people in the state living with a rare disease and their caregivers.

It would consult with rare disease experts, develop policy recommendations for improving access to quality medical care, affordable and comprehensive insurance coverage, medications, medically necessary diagnostics, timely treatment, and other necessary services and therapies.

The RDAC also would perform a host of other functions in support of the 250,000 to 300,000 people living with rare disease in Connecticut. You can view the text of the legislation here.*

Rare disease affects more than 25 million Americans. This equates to 1 in 10 Americans, or one on every elevator and four on every bus, according to the National Institutes of Health (NIH). More than 300 million people worldwide live with a rare disease.

Thirteen members would make up the group that includes the commissioners of public health, social services and insurance or their respective designees

A hospital representative and a physician licensed in medical genetics would be appointed by the governor.

Other members would represent patient advocacy groups, family members or caregivers of a pediatric patient living with a rare disease, a caregiver of a child or adult living with a rare disease, an adult living with a rare disease, a rare disease scientist, a rare diseases physician, and a member of the biopharmaceutical industry.

Kristen Angell, NORD Associate Director of Advocacy, and Lesley Bennett, Volunteer State Ambassador for Connecticut’s RAN, organized the event.

Connecticut’s Lt. Gov. Susan Bysiewicz opened the session saying never doubt the power of advocacy and passionate volunteers that have extensively lobbied her and many others in the statehouse to create a RDAC.

“I have a lot of hope. I know my colleagues in the legislature are people of great compassion who will be working for you.”

U.S. Sen. Richard Blumenthal also offered a statement on the event: “This Rare Disease Day, I’m proud to join the National Organization for Rare Disorders as we renew our commitment to supporting patients, families, and essential caregivers. With robust federal investment, we can and will spur innovation of research, treatments, and cures for those living with rare diseases – saving countless lives in Connecticut and across the country.”

More than a dozen people – advocates, caregivers, patients, doctors, and businesspeople – shared their stories. Many of them are parents of children living with rare diseases, such as rare muscle disorders, rare pediatric cancers, rare genetic disorders, and other diseases that often are described as pediatric Alzheimer’s and juvenile ALS (amyotrophic lateral sclerosis, known as Lou Gehrig’s disease.

Connecticut State Rep. Mitch Bolinsky, one of the legislators in on the meeting, said, “WOW! What an incredible group of advocates. You got us to the finish line and now we just have to get ourselves over it.”