HOPE IN ACTION: A Conversation with Laura Manfre

How did Hope in Focus begin?

In 2013, after our daughter, Sofia, was diagnosed with Leber congenital amaurosis (LCA) IQCB1/NPHP5, the Foundation for Retinal Research (FRR) asked if my husband and I would be willing to raise funds for treatments for her genetic mutation. The FRR was started in 1998 by David and Betsy Brint, whose son had LCA. Little was known then about the disease, and there wasn’t an LCA community when they began. The Brints faithfully stewarded the research and a handful of LCA families to grow that organization into a real community. So, we said yes to the FRR’s request and quickly raised about fifty thousand dollars, largely from our local community in southeastern Connecticut. This success blew us away, but there wasn’t an active research project for Sofia’s gene.

Realizing that so many people were willing to help us, we thought, why not raise funds for all LCA conditions so we can put the funds we raise into use sooner? A broader funding goal would allow us to designate monies for the most promising research and advance projects already in the pipeline. All boats float in a high tide, right? It was the right thing to do. Honestly, I also thought pushing the projects that are further along faster might be the most effective way to help advance the research related to Sofia’s gene. In 2014, we incorporated our 501(c)(3). Setting up the nonprofit made it easier to steward and thank donors. In Connecticut, three people are needed to create a nonprofit. So, my husband, Chuck, myself, and our good friend, Elisse Rosen, founded Sofia Sees Hope, later called Hope in Focus when we changed our name in 2021.

I think it was in early 2017 when David Brint became chair of the board of directors for the Foundation Fighting Blindness (FFB) that the FRR was rolled into the FFB. This change was significant for LCA research because of the FFB’s incredible influence and expertise in research. At the same time, because the FFB serves all forms of blindness, this change opened a gap for focused support for our LCA community. As a single, rare disease-focused organization, Hope in Focus was able to fit right in and fill that gap.

How did your mission/vision evolve?

LCA is a rare disease, which means we are a small community, but we have shared experiences that create a strong sense of unity. As I interacted increasingly with industry and researchers, I learned just how vital it was to have an empowered community equipped to engage with research and biotech to support the advancement of treatments. At the time, it was also apparent that we needed to focus on genetic testing. Genetic diagnosis is still an issue for our community, although we’ve come a long way, and I’m pleased that our work at Hope in Focus has made a real impact in this arena with our fundraising, outreach, and awareness campaigns. When individuals in our community have a confirmed genetic diagnosis and understand how treatments are developed and brought to market, they will also know why we must speak up, be involved in fundraising, and consider participating in patient registries, natural studies, and, hopefully, clinical trials.

When I think about how we’ve evolved, although our mission has stayed the same and is still very relevant, the biggest “a-ha” for me has been realizing that it’s not enough to raise money for research. Understanding the importance of advocacy and our voice in developing our treatments is critical. As a community, we can’t wait for these treatments to fall like manna from heaven. That might be how it works for a lucky few in the future, but that is not how this process works. We must actively participate in registries, natural history studies, patient advisory boards, and legislation. And the community with a voice and a level of representation will garner interest in its rare disease. The more aware and connected we are with the entire ecosystem involved in developing treatments, the greater the opportunity to influence these things.

What have you learned about the research community?

I was surprised by how meaningful it was to meet the people behind the science. As I spoke at events and met the community working on treatments, I stopped thinking about them as a monolith. These are dedicated, caring individuals working daily to benefit people they don’t know. When they have a chance to hear from folks living with LCA, these interactions help inform their work and motivate them to keep at it. We need them to keep working hard to find those treatments, and I think hearing our stories helps. As I experienced these interactions, I realized that to achieve our mission, we needed to facilitate engagement across the entire LCA ecosystem, including everyone impacted by the disease, biotech, regulatory agencies, investors, other nonprofits, and advocacy groups. It takes a lot of people to bring a treatment to market, and we all have a part to play.

Another thing I learned was that an informed LCA community needs to make sure that positive policy decisions are made regarding research and access to treatments. Unfortunately, many legislators don’t understand rare conditions, patient protections, and the actual cost of living with a life-long disease. We must educate our legislators and ensure they make sound, sensible policies.

What helps you see the progress made by Hope in Focus?

I was very fortunate to testify at the FDA AdComm (Advisory Committee) meeting in 2017 for the approval of LUXTURNA®. That opportunity was very emotional and a significant milestone not just for those living with LCA but for all rare diseases and gene therapy. For me, it also underscored the importance of our organization. Two years later, at the LCA Family Conference, we hosted in 2019 in Philadelphia, a woman from Washington State shared the story of her son. Before he turned three years old, he was genetically diagnosed with RPE65 and treated with LUXTURNA, still the only genetic treatment for LCA available on the market. Wow! The room went silent. We were talking about getting to this point, but I was surprised it was already happening to someone in the room.

Meanwhile, there were families in that room who were still unable to get a genetic diagnosis. Hearing about her son’s early diagnosis and treatment was incredible and gave us all hope. I want to hear more of these stories for all genetic variants of LCA. Another exciting development is the growth of our international community. At our LCA Family Conference in 2023, we had folks attend from all over the world, including a family living in China who told us about their database of 130 families with the CRB1 genetic mutation. Everyone was shocked that such a large group was identified for a single gene. LCA is a rare disease, making it hard to find and connect people, and here were 130 families with the same gene. Again, wow!

What do you hope for the future?

When we started Hope in Focus, it didn’t seem like anything was happening with research for LCA from my perspective as a parent. But under the surface, research was moving forward, and many dedicated folks in the LCA ecosystem were hard at work. Ten years later, we have a treatment on the market, LUXTURNA®, with four potential treatments currently in the clinic, several preparing for trials, and multiple gene-agnostic therapies in development. There is so much hope as the science is advancing. On the other hand, it has been SEVEN YEARS since I testified before the FDA, and LUXTURNA was approved for just one of our LCA genes, and there are still no new treatments on the market for other LCA variants. We need to keep the pressure on.

What do I hope for the future? This year, Hope in Focus is engaging in strategic planning to ensure that, as an organization, we are prepared and able to meet the changing needs of our LCA families and individuals as science, regulation, and industry evolve over the next 10+ years. When I started ten years ago, LCA research was a ripple, and now it feels more like a big wave. Hope in Focus needs more help to row the boat as that wave grows, including program funding, volunteer support, and dedicated staff. As we plan for the next ten years, we must define what this looks like and what it will take to get there. I also hope that Hope in Focus will participate in more Advisory Committee meetings for drug approvals. I’m disappointed I only got to testify at one of these events! How cool would it be if we could shift from a focus on supporting the advancement of treatments to market to helping members of our community as they evaluate whether or not they want to choose a treatment and then supporting them through that process? (Make sure to read Jack’s story.)

After creating Hope in Focus, have you asked yourself, what have I done?

Yes, I ask myself that question all of the time. At the very beginning, I was one person doing almost everything. Managing a startup nonprofit is exhausting. Today, we have a small but mighty team that includes one full-time employee, but I’m still volunteering at almost the same level as in those early years. Why? Because Hope in Focus is like tapioca; it just keeps growing. I’m very grateful for all of the volunteers and our incredible staff. We’ve connected with and helped so many people from whom I’ve learned so much. While growing Hope in Focus has been very demanding, it also fills my cup, and I feel so lucky to be a part of it.

What other thoughts would you like to share?

Hope in Focus has given me a sense of control over something I had no control over and felt utterly overwhelming. I think our work does the same for other parents and individuals living with this rare disease. I see how we are helping folks today, and I know that we’re helping to advance treatments that will help someone in the future. Hope drives action, and as we keep pushing forward, I’m excited to see what the next ten years bring for our community and Hope in Focus.

Hope in Focus Brings Voices of People Living with LCA Directly to the FDA

Allison Wolf, whose 9-year-old son Elliot lives with the encroaching blindness of Leber congenital amaurosis (LCA), spoke directly to staff from the country’s regulatory agency to help them understand the dire need for treatments for the rare inherited retinal disease.

“Elliot’s eyes are dying, Allison said. “They are dying, and we have nothing to help slow down the progressive loss of his eyesight,” she told the Foo d and Drug Administration (FDA).

“What would a timely and effective treatment mean? The whole world,” the mother of four said.

Allison and five others affected by LCA shared their stories with the FDA during a recent Patient Listening Session hosted by Hope in Focus.

We brought together the voices of people living with LCA, caregivers, and a clinician treating people with LCA to FDA staff members in a 90-minute online meeting Oct. 30, 2023. Simply put, we wanted the FDA to truly hear our community’s voices.

Our year-long planning resulted in a successful session to help regulators understand patient/caregiver experiences related to LCA. We requested the meeting to raise awareness with FDA staff about clinical differences of LCA genotypes, share patient experiences of LCA’s impact on the quality of their lives, given the scarcity of treatments, and communicate the extraordinary significance of vision stabilization for patients.

Raising awareness is key to advancing research

People in our community struggle daily to find ways to cope and try to live normal lives in a sighted world. Still, they never give up hope for new treatments and the possibility of a cure. As an advocacy organization, one of our biggest challenges is creating awareness of LCA.

Courtney Coates, our Director of Outreach and Development, introduced the Hope in Focus mission and said LCA affects about one in 33,000 people and presents early in life, resulting in total blindness. Twenty-seven genes have been identified to cause LCA, with treatment available for one form, while a handful of others are in clinical trials.

Co-founder and Board Chair Laura Manfre said as the parent and caregiver of their daughter Sofia living with LCA, raising awareness, searching out new treatments, and providing support to the growing LCA community became the mission of Hope in Focus.

Laura said she wanted to underscore the goals of treatment, in particular around the stabilization of vision for Sofia and others with LCA.

“While vision restoration would be fantastic, having access to a treatment that stabilizes her vision would be huge for her. Not having to constantly change her accommodations for her changing vision is a huge win, and not having to fall asleep every night worried that the next morning might be the one she wakes up without any vision at all. That would be life changing.”

Sharing a chart showing seven current clinical trials, she explained two are not recruiting at this time, two have been discontinued, and all seven represented only four LCA genetic variations.

“So, there is still a lot of work to be done to advance potential treatments.”

Caregivers and people living with LCA tell their stories

Six people from our community shared their experiences.

Elliot Wolf wearing red glasses and a red shirt — Elliot Wolf

Allison Wolf, who is 45 and from North Dakota, said doctors diagnosed her son Elliot with LCA13 (RDH12) when he was 6, and as he gets older, her challenges also grow.

“Nobody knows how to raise a visually impaired child. I must be taught. I must teach him the sighted world, while also dealing with the challenge of teaching him the non-sighted world,” she told agency staff. “My heart hurts when I hear Elliot say, ‘I just want to be done with all this work and I just want to play.’”

***

Mohamed Farid of Illinois is a 36-year-old entrepreneur, diagnosed with LCA5 at 40 days old. His mother quit her job to take care of him, and they moved back to Egypt. Preserving his sight concerns him the most, and his greatest fear is the risk of injury.

“For new treatments,” Mohamed told the FDA, “the first thing I would look for is something to stop any degradation – I sense that my functional vision has degraded slightly over time and would imagine there is something going on with my retina, but do not know.

I have been told by doctors that I will lose my sight in the next two to three years ever since I was 5, and that lack of a prognosis is a killer. Following conservation, I care most about night blindness, then field of vision. …

“I was lucky to have a huge support network of people, who went out of their way and had a lot of energy and stress tolerance. This does not mean that life was easy or that I would not want a cure, even a partial cure would be life changing. It does mean that the cost of LCA is high, but barely bearable.”

***

Joy Goodwine, 40, of New York is the mother of 7-year-old Jordynn, diagnosed at age 1 with LCA2 (RPE65), and received a new diagnosis last year of LCA1 (GUCY2D). She always wanted Jordynn to have some sense of normalcy.

Jordynn Erwin in pink dress with a hot pink background — Jordynn Erwin

“I’ve always asked family and friends to treat her like any other child,” Joy said. “I do not want people to feel sorry for her and I do not want her to have any special treatment because of her

visual impairment. Jordynn is being raised to know that she is capable of doing anything she wants with limitations…

“What I fear most as a parent with a child living with LCA is I worry that her kindness and vulnerability will lead to unwanted interactions when she gets old enough to go off on her own, or her eyes get worse if treatment is not available.”

***

Linda Wirth is 76 and lives in Colorado. Her vision loss remained a mystery until her diagnosis of LCA10 (CEP290) at age 68. As a child, she learned about the world around her by touching things and holding them.

“My family often told me, ‘Don’t touch that! You will break it. Don’t act strange. People will stare at you.’ So, I began to fake it, pretending I understood things which I did not in order to get along and not appear any different.”

One doctor early on told her: “You are blind! What do you want me to tell you? If you are looking for a miracle, there is none.”

A retired clinical social worker, Linda’s been angrily dismissed from jury duty and job interviews, ignored by waitstaff, and questioned whether she deserved to be a parent.

“Just as many differently abled folks, I have encountered individuals with various stereotypes and prejudices.”

***

DJ Broadbin of Connecticut is a 34-year-old mother and caregiver to 5-year-old Jace, who was diagnosed with LCA4 (AIPL1) at 10 months old. Through a Hope in Focus connection, she succeeded in getting compassionate use treatment in the UK for Jace. The treatment, which applied only to his specific gene mutation, has restored some of his sight in one eye.

“No matter what happens with his vision or developing new treatments,” DJ told the FDA, “I remain steadfast in having the same goal I had for Jace since the very second I found out I was going to be a mom – I just want him to be happy. And I will continue to fight for his inclusion in this world to make sure that he always is.”

She often finds herself exhausted by the constant stress of being a caregiver.

“I also wish sometimes,” DJ said as her voice broke, “I just got to be a mom. Not a medical coordinator, an occupational therapist, and a Teacher of the Visually Impaired all rolled up into one. Just mom.

“But then I think about all the things that Jace’s diagnosis has given me personally: Clarity. Patience. Compassion and empathy in a way that I myself was too blind to see in those earlier days.”

***

Mirielle St. Arnaud is 16 and lives in Illinois. She was diagnosed with LCA (IQCB1/NPHP5) at 6 months old. Her early diagnosis was possible because her older brother had been diagnosed with LCA.

Mirielle worries about her safety and struggles to fit in with her classmates because she misses social cues. She hopes her fairly stable vision will not get worse.

She shared a wish list with the FDA that included personal independence, the opportunity to participate in sports, and more certainty about achieving the career of her choice (she dreams of being a lawyer).

“Some of the more significant challenges I face because of visual impairment relate to jobs and getting hired. It takes longer for me to learn certain skills at a job. I have to rely on others when out in public, especially when traveling. I also struggle to find accommodations for my impairment. It seems that other people know my needs better than I do.”

***

Our representative clinician, Rachel M. Huckfeldt, MD, PhD, of Massachusetts Eye & Ear, spoke about the difficulties of diagnosing and managing LCA and the small number of clinical trials. Identifying the responsible genes can be difficult, and the small number of patients severely limits opportunities for clinical trials.

Questions asked by FDA staff members focused on a few common themes: Have you participated in clinical trials? What are the key impediments to clinical trial participation? What are your deal-breakers to participation? What would a successful treatment look like to you?

One result certainly not on the agenda was the deep emotional impact of the stories shared by those living with LCA and caregivers. The session manifested itself as a profoundly moving event.

A full summary of the FDA Patient Listening Session will be available on our website.

Hope in Focus Grateful for 2023 Dinner in the Dark Success

So much more than a typical fundraiser, the 8th Hope in Focus Dinner in the Dark we advertised as “a unique sensory experience,” gave guests just that and much more Saturday, Oct. 14, 2023, at the Mystic Marriott Hotel & Spa in Groton, Connecticut.

Dinner in the Dark afforded the opportunity for guests to experience their dinner in a different way – wearing blindfolds. For a short time it offers a small taste of what it might be like for someone dealing with a rare retinal disease. This key fundraising event supports our mission of “Seeing a cure for blindness,” as we advocate for people living with Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs).

Attendees sitting at table with their blindfolds on

Hope in Focus counted 273 attendees this year, with the event raising more than $200,000, a record amount for our annual fundraiser.

The evening is about bringing people together to connect with the mission of Hope in Focus, as we work to transform the lives of those living with blindness caused by LCA and raise funds to support research treatments.

Our hope for those treatments is becoming a reality through the half-million dollars we have raised throughout the years with the vital support from contributors and from people like those attending the dinner.

These essential dollars fund myriad retinal research studies here and abroad, and they ensure access to free genetic testing, a critical step toward finding retinal-disease treatments.

“Even as science advances, we still have only one treatment on the market today for just one form of LCA,” said Laura Manfre, Hope in Focus Co-founder and Board Chair. “We need to do better. We need to continue advancing the science, but also move the science from the lab and the clinic to the community waiting for treatments.

“It is with deep gratitude,” she said, “that we thank all the people who came out to support our efforts to improve the lives of people living with rare retinal disease and help advance research for treatments. We could not do this without you, and we are forever grateful for your contributions toward our mission.”

Courtney Coates, Director of Outreach and Development, shared with the guests Hope in Focus’ work in delivering updates and research progress in our newsletter, across social, in our Let’s Chat About webinar series, and at our 3rd LCA Family Conference this summer, when we welcomed LCA families from across the country, as well as Canada, Mexico, China, and Turkey. She also shared news about our then-upcoming hosting of an LCA Patient Listening Session with the Food and Drug Administration.

Our zebra, Luca Priebe, with Courtney Coates

“Tonight for a brief time, you will get a taste of what it might be like to live with vision loss, including some of the social challenges that accompany it,” Courtney said. “We hope this will move you to join our journey, as we continue our work to fund research to treat blindness caused by LCA and expand our advocacy activities.”

Courtney, our sole full-time Hope in Focus staff member, thanked each of our sponsors, and there were many. Click here for a complete list of our 2023 Dinner in the Dark sponsors.

She also thanked our Dinner in the Dark Committee members – without whom the event would not have been possible – for volunteering their countless hours behind the scenes.

Laura described for newcomers the origin of Hope in Focus and its mission. She founded the organization in 2014 with her husband, Charles Priebe, and close friend Elisse Rosen, having been brought into the rare retinal disease community by her daughter Sofia, who was diagnosed with LCA at age 2.

Heading into its 10^th year, Hope in Focus has grown into a global patient advocacy organization, supporting the LCA community and researchers seeking cures and therapies for rare inherited retinal diseases.

Laura introduced the evening’s key presenter, Dr. Daniel Chung, as a “rock star.” Dr. Chung is Chief Medical Officer for SparingVision, an ocular genomic medicine company. His work focuses on therapies to combat blinding diseases. He made a point of praising the courage of participants in clinical trials. These patients offer themselves to science, not knowing what the result may be, or if there will be any result at all.

“The real rock stars,” Dr. Chung said, “are those who say, ‘I’m going to be part of a clinical trial.’”

The final speaker before dinner was probably the most instructive. Sofia Priebe spoke via a video presentation to provide tips for a successful Dinner in the Dark experience.

Sofia advised on such techniques as determining which side of your knife is sharp, using utensils to gently explore the food on your plate, and remembering to always identify yourself and the person you’re speaking to in conversation at the table.

Now a junior at college, she spoke with the poise and grace of someone beyond her years. In her final tip, perhaps the most important, she advised: “Food to face, not face to food.”

Roger Nicholson, Executive Chef of the Mystic Marriott Hotel & Spa, prepared the dinner presented in four courses. To see the menu, please go to: https://old.hopeinfocus.org/whats-for-dinner/

Each course tasted delicious, and Sofia’s advice was put to good use as well, with one participant heard to exclaim, “It’s a square plate! Use the grid system!”

Image of two attendees holding up wine glasses.

Attendee Karen Clarke of Guilford said navigating a meal while blindfolded is challenging and humbling.

“The experience gives you a small glimpse into the challenges so many deal with every day. It’s a great motivation for us to help with research – and be thankful for our own sight when the blindfold comes off.”

Rosalie and John Maxham of Stonington attending Dinner in the Dark for the first time.

“We came away appreciating this organization devoted to helping find a cure for a disease we never knew existed, and we were very happy to lend our support to this zebra.”

The live auction, requiring no blindfolds, followed dinner, with Master of Ceremonies Mike O’Farrell auctioning up for bid items and experiences, a list of which can be found at: www.hopeinfocus.org/get-involved/dinner-in-the-dark/live-auction

After sweets for dessert, guests headed for the dancefloor for music by The Cartells.

We at Hope in Focus thank all the participants and faithful sponsors of Dinner in the Dark and look forward to an exciting event in 2024.

2023 LCA Family Conference: Developing LCA Treatments

Luxturna®, the only approved treatment for one of 27 identified forms of Leber congenital amaurosis (LCA), cost $500 million to develop and took more than 12 years to come to market.

With such an enormous investment in time and money, it would make sense to use that same platform for developing new treatments to improve vision or halt progression of blindness.

But that’s just not how it works, said Chad R. Jackson, PhD, Senior Director of the Foundation Fighting Blindness Preclinical Transitional Acceleration Research Program.

Every individual clinical study must complete a set of rigorous requirements – which cost time and money – to receive regulatory approval from the Food and Drug Administration (FDA).

The Foundation’s translational research program steps up the pace of preclinical studies toward clinical studies involving humans through proactive management and industry-level advice to drive research leading to prevention, treatment, and vision restoration for degenerative retinal diseases.

A Hope in Focus partner, the Foundation has raised nearly $900 million since its founding in 1971 and funds more than 90 programs worldwide, including no-cost genetic testing and the My Retina Tracker® patient registry. The Foundation also launched a Retinal Degeneration Fund (RD Fund) to help accelerate life-changing outcomes for people with retinal degenerations through direct mission-related investments in therapeutic companies.

Chad and other presenters shared information about drug development, gene therapies, and non-gene therapies during two sessions of the Hope in Focus 2023 LCA Family Conference* in Indianapolis this summer.

More than 100 people attended the forum to hear the latest in LCA research and to network with families living with LCA and other rare inherited retinal diseases (IRDs).

Bringing a drug from inception to market takes 10 to 15 years, Chad said, and costs tens and tens of millions of dollars. He said bringing a developing drug from preclinical studies to the FDA requires three steps:

Identify your target to know what you’re seeking to do; conduct invitro studies by expressing patient cells in a lab or as it’s referred to, retinas in a dish; and perform animal-model studies, which save time and money to determine whether emerging therapies are safe and perhaps ready to move toward clinical trials using humans.

Gene-Agnostic Therapies

Chad moderated a panel discussion about research moving beyond single-gene correction to gene-independent therapies to help delay progression of blindness or restore levels of vision.

Kiora Pharmaceuticals’ Chief Development Officer Eric J. Daniels, MD, MBA, discussed the company’s first-in-human study for a non-gene therapy treatment for retinitis pigmentosa (RP), a group of inherited eye diseases that cause progressive vision loss. It is characterized by the gradual death of light-sensitive photoreceptor cells in the retina, known as rods and cones, responsible for converting light into neutral signals sent to the brain.

Dr. Daniels said his company’s technology shifts retinal ganglion cells from their off state, in which they respond to decreases in light. Kiora has discovered a way to shift these cells into their on state in the presence of light through channeled photoswitch molecules.

According to Kiora, the mutation-agnostic treatment has the potential for use in any of the various genetic forms of RP, as well as other retinal degenerative diseases; its intravitreal injection allows for more consistent and tolerable administration, and the small molecule can be manufactured and provided to patients at a much lower expense than the $450,000 per eye cost of Luxturna.

Huma Qamar, MD, MPH, CMI, the head of Clinical Development and Medical Affairs for Ocugen, discussed the biotech’s work on treatments for LCA10 (CEP290), RP, and other IRDs. One of their clinical trials involves a novel gene therapy, OCU400, consisting of a functional copy of a nuclear hormone receptor gene delivered to target retinal cells using an adeno-associated viral (AAV) vector. Expression of this receptor within the retina may potentially help stabilize cells and rescue photoreceptor degeneration, Dr. Qamar said.

Ocugen demonstrated the potential of a novel modifier gene therapy to elicit broad-spectrum benefits in early and intermediate stages of RP and LCA, based on animal studies, showing the potential for a mutation-agnostic treatment.

Since the conference, Ocugen reported an update on its Phase 1/2 clinical trial for OCU400 for 12 patients who had follow-ups from six to 12 months after a subretinal injection in one eye. The developing drug had a favorable safety profile in this trial phase. Also eight of the 12 patients showed stabilization or improvement in the visual function measures of best corrected visual acuity, low-luminance visual activity, and navigating a multi-luminance mobility test.

The trial is currently enrolling patients, including pediatric patients with LCA10.

Gene Therapies

In the conference’s final session, moderated by Foundation Vice President of Science Communications Ben Shaberman, four panelists discussed their work on LCA gene therapies.

Shannon Boye, PhD, Co-Founder, Director, and Acting Chief Science Officer of Atsena Therapeutics, said the road to drug development is long and bumpy. She helped design early studies on LCA1 (GUCY2D) in 2001.

With the process going so slowly, Shannon reached out to then-Foundation CEO Ben Yerxa, who helped push her and her husband into starting their own company.

In 2019 doctors dosed the first patient. Earlier this year, in a Phase 1/2 clinical trial, their LCA1 gene therapy, known as ATSN-101, showed clinically meaningful improvements in vision at the highest dose with no drug-related serious adverse events at six months after treatment.

At Opus Genetics, Chief Scientific Officer Ash Jayagopal, PhD, discussed the biotech’s progress for various programs in, or advancing toward, early-stage clinical trials.

Opus, headed by CEO Ben Yerxa, PhD, is the first spin-out company internally conceived and launched by the Foundation’s RD Fund. The Fund’s purpose is to accelerate advancing research into gene therapy for several forms of LCA and other retinal degenerative diseases.

Opus’ most advanced program for LCA5 (lebercilin), OPGx-LCA5, is dosing patients, while two other LCA programs involving LCA13 (RDH12) and LCA9 (NMNAT1) are in preclinical development.

Thomas Mendel, MD, PhD, talked about his research at The Ohio State University, where he is Assistant Professor of Ophthalmology and Vitreoretinal Surgery at the university’s Havener Eye Institute, Department of Ophthalmology & Visual Sciences. He is building a research program to develop and implement gene therapies for Professor of Ophthalmology and Vitreoretinal patients with inherited retinal disease.

The goal is to build a translational lab with a team and accelerate development and clinical trials with gene-based treatments.

Bikash R. Pattnaik, PhD, told the audience about his work at the University of Wisconsin-Madison (UWM), where he is a professor and Clinical Director for Electrophysiology in the departments of Pediatrics, Ophthalmology, and Visual Sciences.

This summer, the National Institutes of Health awarded UWM a $29 million grant to develop gene-editing therapies for two inherited retinal conditions: LCA16 (KCNJ13) and Best disease. Bikash said the LCA16 treatment in development could be in clinical trials next year.

*Please go to our Hope in Focus website to see our previous three stories detailing sessions from our 2023 LCA Family Conference. Click here to see a video about the conference.

2023 LCA Family Conference: Living with LCA–Panelists with varied vision share life successes and challenges

Tami Morehouse is grateful for improved vision after undergoing groundbreaking gene therapy treatment at age 44 for LCA2 RPE65, but at times she still is sad and disappointed at the difficulties presented to her as a person with some functional vision, but who cannot see well.

Mohamed Farid found life living with LCA5 more challenging as a child than as an adult, especially before screen readers and other assistive technology. The young professional also remembers growing up and his grandmother spending a lot of time convincing him he couldn’t be a pilot.

Mirielle St. Arnaud, a junior in high school living with LCA caused by a mutation in her IQCB1/NPHP5 gene, tries to get involved with clubs and activities to ward off struggles with socializing. She learned to adapt to change and said her experiences with vision challenges have been good.

Tami, Mohamed, and Mirielle talked about their day-to-day lives, challenges, and feelings at our 2023 LCA Family Conference* in Indianapolis in late June. They took part in a panel discussion called Living with LCA, moderated by Beth Borysewicz, an educational consultant with the Connecticut Department of Aging and Disability Services with Bureau of Education Services for the Blind.

These three people – an LCA research pioneer, a young professional, and a high school student – help illustrate the manifestation of research advances and assistive technology in the last decade or so.

Here is what they shared with more than 100 people convened for the third Hope in Focus LCA Family Conference.

***

Tami Morehouse

Tami, 59 and from the Cleveland area, is thankful to see with more brightness following her participation in a pioneering clinical trial for what now is known as LUXTURNA®, the only federally approved treatment for one of the 27 identified forms of LCA – LCA2 RPE65.

She gained some vision in 2009 and 2010, when she received the treatment under development by Spark Therapeutics.

“My whole world was a lot brighter,” she said.

She could see a cup on the table, gorgeous sunsets, the lush green of spring, and details in the faces of her three children. It also improved her parenting skills.

“Mom can see things now,” she joked. “It’s bittersweet in our world.”

She also feels she lives in a kind of limbo between seeing and not seeing. She wished and still wishes the public would be more receptive to her being between having sight and not having sight, rather than completely blind.

Tami’s world has widened, and she enjoys much happiness since receiving the gene therapy. She is a Hope in Focus Ambassador, working with our Family Connections program, reaching out to people living with LCA, offering them comfort and kindness. The research pioneer works as an information and referral specialist for 211 in Ohio.

People in the LCA community, like others dealing with a rare disease, experience anxiety, depression, and social isolation.

Tami opened up at the conference, sharing struggles to maintain mental wellness.

She experienced a lot of awkward moments and has worked at becoming comfortable with who she is as a blind person.

“There are so many times when I’m very sad and disappointed about my limitations. There are a lot of barriers in the way and that’s hard to take.”

She misses experiences she could have had with her children and husband and parents.

“Those are just facts of life. Those are my facts, but I think many others go through the same.

“Sometimes we just feel the burn.”

***

Mohamed Farid

Mohamed Farid navigates life with LCA deftly, now that he is an adult.

“It’s harder growing up. It’s easier when you’re older.”

Life became easier with innovative technology, such as screen readers and other optical character-recognition technology that extracts and converts data into a machine-readable form.

“It’s all about assistive technology,” he said.

The 36-year-old founded MKF Continuity, a middle-market investment firm in Chicago. He earned an MBA from Harvard Business School.

There was a time when he was running away from his blindness.

“Now, I’m just ‘whatever’. I need to be independent. It’s important for my dignity. I don’t want to be relying on people.

“Every once in a while, I think the world is unfair,” he said, but over time he’s developed self-acceptance and is at peace with his blindness.

He compared his moving through life now not even thinking about his blindness to his perception of his vision as a child.

“My grandma had to spend a lot of time convincing me I could not be a pilot.”

In contrast, as an adult at his workplace, people think he can create slide presentations.

Mohamed said his blindness has made him strong, describing himself as “alert, scrappy, and resilient.”

***

Mirielle St. Arnaud

Mirielle St. Arnaud, a 16-year-old from the Chicago area, said she’s dealt with people who assume she’s not a capable person.

“We’re probably more resourceful than you think,” she said.

Mirielle is a junior in high school, where she runs on the cross-country team with a guide and is a captain of the Congressional Debate team.

She learned to advocate for herself and set boundaries for others.

Mirielle worked at her difficulties with socialization at school by getting involved in the blind and sighted communities, whether through summer camps or extra-curricular activities, and by meeting as many people as she can.

“At some point, you’ll find your people who will understand you.”

She characterizes her ability to see as “Swiss-cheese vision.”

At school, she collaborates with an advocate throughout the year, using an Independent Education Plan as a guide.

Mirielle said vision specialists collaborating with her schools have been especially helpful along the way. She’s worked with Teachers of students with Visual Impairments, who are educators with expertise with the visually impaired, and Orientation and Mobility specialists, who teach safe and effective navigation through environments.

“I’ve had pretty good experiences,” she said.

***

Wrapping up the session, panelist Mohamed Farid left the audience with this message:

“Our journey can be bumpy. Don’t ever give up hope.”

*Please go to our Hope in Focus website to see three more stories detailing sessions from our 2023 LCA Family Conference. Click here to see a video about the conference.

2023 LCA Family Conference: Advocating for Treatments

Here’s what you need to know about advocating for advanced treatments for Leber congenital amaurosis: Get genetically tested, get legislatively connected, and get enrolled in a patient registry.

The Hope in Focus 2023 LCA Family Conference* panel on Advocating for Treatments repeatedly returned to this action trio to move treatments forward for this rare inherited retinal disease (IRD) affecting about 8,000 people in the United States and 160,000 worldwide.

Jonathan Stokes, Senior Director of Patient-Centered Outcomes Research with the biopharmaceutical company AbbVie, moderated the five-member panel at the June 23-24, 2023, LCA family-centered conference in Indianapolis. This session marked the first of four for more than 100 people gathered at the conference.

Genetic Testing is Critical

Emily Place, Senior Genetic Counselor and Manager of Genetics and Genetic Counseling at Massachusetts Eye and Ear, said the first place to start is to get genetically tested, a process becoming easier with time. An open-access genetic testing program managed by the Foundation Fighting Blindness creates a smoother journey to finding the specific gene causing a mutation resulting in LCA or other IRDs.

Your new confirmed genetic diagnosis opens the door to advocacy groups and researchers working to develop treatments and cures for blindness.

The National Society of Genetic Counselors (NSGC) offers in-depth genetic testing information, including a search tool to help find a certified genetic counselor in your area.

Emily said listening to the voice of the patient is the way to move research forward. And, in the rare inherited retinal disease world, that begins with genetic testing and genetic counseling.

A genetic test provides one of three results: Positive, negative, or inconclusive.

A positive result means the test found mutations in a specific gene that can identify the cause of vision impairment.

A negative result means the test could not identify a specific genetic cause for the disease, but it does not rule out a retinal disease diagnosis.

An inconclusive result means the test didn’t find helpful information about the gene in question. Because it can be difficult to distinguish between a disease-causing gene and a harmless gene variation, follow-up testing or periodic review of the gene over time might be necessary.

Emily said it’s important to stay connected with your genetic counselor for support along the way, especially with an inclusive result. As the knowledge base of genetic data grows, future tests could garner more definitive results.

Genetic testing information can be found at Hope in Focus, which has contributed more than $200,000 to help support the Foundation’s free access to genetic testing.

You’ll find information on the Foundation’s website under the Genetic Testing section, where you can download their detailed resource booklet, “Genetic Testing for Retinal Degenerative diseases: Information and Resources for Affected Individuals, Families and Health Care Providers.”

Empower U.S. Senators and Representatives to Advocate for LCA

Our panelist from the U.S. Food and Drug Administration agreed with importance of genetic testing. Wiley A. Chambers, MD, Supervisory Medical Officers of the Office of New Drugs for FDA’s Center for Drug Evaluation and Research, also advised bringing information to Congress for action. He and his eight-member team have signed off on 200 approvals of new drugs.

“The best place you can make an important impact is to talk with your representatives and senators,” Dr. Chambers said.

A good place to start is with their staff of congressional aides, who can synthesize and relay relevant information to lawmakers.

He noted a key change at the FDA in the 1960s that informs the current drug approval process.

In October 1962, Congress passed the Kefauver-Harris Drug Amendments to the Federal Food, Drug & Cosmetic Act, which contains regulatory requirements defining the FDA’s level of control over these products. Before marketing a drug, firms still had to prove safety; now they also need to provide substantial evidence of effectiveness for the product’s intended use. This requires adequate and well-controlled studies, and, before marketing, the FDA needs to specifically approve a marketing application, according to the FDA.

Dr. Chambers emphasized that any clinical trial needs to show what the product is going to do to benefit a particular individual. He cited one of the endpoints or outcomes – early in Spark Therapeutics‘ gene therapy trial – that enlarged the size of the pupil.

“So what?” he said. “That’s not an endpoint that is meaningful to any individual.”

An endpoint of value would improve vision, slow, or stop vision loss, and help with daily activities.

Panelist Jacose Bell, Senior Patient Advocacy Lead at Spark Therapeutics, said the clinical trial at issue needed light as a factor as an endpoint.

Spark redesigned its trial to include a relevant endpoint instrumental in demonstrating how voretigene neparvovec could improve vision in LCA2 RPE65 patients, leading to the approval of LUXTURNA®. The endpoint – a multi-luminance mobility test (MLMT) – measured functional vision or how a person navigates in a vision-related activity across a range of light levels in daily living.

Engage state lawmakers to advocate for LCA advances

Reaching out to congressional aides is important, and even before taking that action, people can inform and raise awareness of the needs of the LCA and IRD community on local and state levels. This means calling, writing, or emailing your governor and state representatives and senators. It means acting and being participatory.

The National Organization for Rare Disorders (NORD) runs a state-by-state Rare Action Network that works to establish Rare Disease Advisory Boards or RDACs. Connecticut, headquarters for Hope in Focus, recently became the 24th state establishing a council specifically to address the complexities of living with a rare disease (including LCA and other IRDs), caring for someone with a rare disease, gaining access to treatment, and getting better insurance coverage.

The RDAC gives patients, families, caregivers, healthcare providers, advocates, researchers, and other stakeholders the opportunity to make formal recommendations to state agencies and the legislature to improve the lives of people living with rare disease and their caregivers.

Click here to find out if your state has an RDAC or is developing one and you would like to help make it a reality.

Lighthouse Guild also provides medical assistance and social support to people who are blind or visually impaired so they can fulfill their goals and live with independence.

EveryLife is another resource providing help for people living with rare diseases, including LCA and other IRDs.

Results of surveys filled out by people living with LCA and other IRDs also help define areas in need of advocacy, resources, and research.

LCA and IRD Patient Registry – My Retina Tracker®

Panel member Laura Manfre, Board Chair and Co-Founder of Hope in Focus, centered on patient registries as a driving factor in advancing treatment.

“MRT, MRT, MRT,” she said as a mantra to the group. MRT – My Retina Tracker® – is an online, confidential registry of people with rare retinal degeneration, including those with LCA or other IRDs.

Foundation Fighting Blindness launched and manages the registry with the purpose of enabling people with inherited retinal degenerative disease, their doctors, and researchers to actively collaborate in the research process.

To optimize the power of MRT, registrants should seek a genetic diagnosis, which the registry facilitates by making registrants eligible for free genetic testing.

Patients share information about the history, progression, and personal impact of their disease, they authorize their doctors to add their diagnosis and clinical information to their profile, and they take part in research studies when identified and contacted through MRT by researchers as potentially good subject for their studies.

The larger and more detailed the registry, the more beneficial the data becomes to doctors and scientists in helping advance research.

Another specific way to bring research to the labs and new treatments to market is through patient advisory councils established by biotechnology companies.

Panelist Jill Dolgin, PharmD, Executive Director of Global Patient Advocacy & Scientific Management for Beacon Therapeutics, said she even brings people into the lab to explain in plain language the complexities of clinical trials. This brings a broader understanding and familiarity to people who potentially might participate in trial research, including natural history studies of patients.

“You’re the experts,” Jill told her audience. “We’re not.”

Natural history studies identify demographic, genetic, environmental, and other factors shaping the drug development process. They give scientists and researchers a better estimate of the prevalence of the disease, help identify potential biomarkers, affect clinical outcome assessments, and determine the feasibility of established assessments for clinical trials.

Finding people to take part in research into a rare disease is inherently difficult, so reaching out to patients and helping them learn about the process helps expand the pool of potential participants.

Dr. Chambers says he hears about the difficulties of natural history studies from both sides, with researchers saying they can’t find patients to take part in the study, and patients saying they can’t find the study in which to participate.

“The starting point for each of these is genetic testing,” he said.

***

Hope in Focus would like to thank this session’s moderator, Jonathan Stokes, and its panelists, Emily Place, Dr. Wiley A. Chambers, Jill Dolgin, and Jacose Bell.

We are also grateful for the support of our sponsors in helping bring to fruition a gathering of such importance and relevance to the LCA and IRD community. Thank you, Spark Therapeutics, Foundation Fighting Blindness, MeiraGTx, Janssen, Atsena Therapeutics, Ocugen, and Kiora Pharmaceuticals.

*Please see our Hope in Focus website for three more stories detailing sessions from our 2023 LCA Family Conference. Click here to see a video about the conference.

Hope Rules at 2023 Hope in Focus LCA Family Conference in Indianapolis

Our 2023 LCA Family Conference in Indianapolis offered many reasons to feel hopeful about more retinal disease treatments coming to fruition and in less time than the dozen or more years it’s taken to bring a therapy to market, despite the deep complexities and tremendous expense of researching and developing LCA therapies.

More than 100 people gathered in late June from around the globe in Indianapolis for the Hope in Focus LCA Family Conference – making friends, meeting researchers, and establishing connections to help better navigate life with Leber congenital amaurosis, a rare inherited degenerative retinal disease.

The conference succeeded in its goal of creating an ideal environment for thoughtful and interactive exchanges of knowledge, ideas, and viewpoints in sessions focusing on research, future treatments, advocacy, shared stories, and connections with people traveling similar journeys.

The Hotel Omni Severin’s mezzanine on Friday, June 23, to Saturday, June 24, buzzed with the sounds of LCA families socializing with conference speakers and families, kids with LCA running around having fun, and grownups meeting other adults living with the rare disease.

As one caregiver said of the event: “This is fantastic! I’m getting answers to questions I didn’t even know how to ask.”

People from the Midwest, the rest of the country, and around the globe – from Canada, Mexico, Turkey, and China – converged in the Racing Capital of the World to hear from LCA families, retinal doctors, researchers, advocates, and representatives of the biotechnology and pharmaceutical industries.

A mix of kids and caregivers attending the 2023 Hope in Focus LCA Family Conference in Indianapolis

Navigating the LCA Ecosystem

Laura Manfre, Board Chair and Co-Founder of Hope in Focus, welcomed the group to our third LCA Family Conference, and its first in four years because of in-person social limitations caused by the COVID-19 pandemic. The next conference is set for 2025.

Advancing treatments for LCA is part of an ecosystem many may not have thought about before being thrown into it with a rare disease diagnosis, Laura told the group.

“No one asked to be a part of this disease or came into this knowing how to navigate this journey for their child, their family, or themselves,” she said. “We are all figuring it out as we go, and the more we can connect with one another, the better we are able to learn and share and support one another.”

Hope in Focus gathered representatives from this LCA ecosystem – from pharma and biotech, to regulatory to research and healthcare, with each stakeholder playing a critical role necessary to developing treatments for LCA.

“We all need one another to make this work.”

Even having the kids at the conference get together for a day at the Children’s Museum of Indianapolis, while their parents attended panel discussions, marked a milestone of sorts for children with LCA.

“How often does that happen that sighted and visually impaired siblings get to be in a group together like that? It’s really cool.”

Laura, her husband, Charles Priebe, and their good friend Elisse Rosen founded Hope in Focus nearly 10 years ago to raise funds for research, after doctors told Laura and Chuck their 11-year-old daughter Sofia had LCA17 caused by a mutation in her IQCB1/NPHP5 gene.

Laura explained Sofia’s absence from the conference, where she had planned to talk about living with LCA.

“She is now 20, a rising junior in college, and her vision is getting worse,” Sofia’s mom said. “Yes, she was supposed to be here and be on a panel, but she finally, after years of waiting, got a guide dog and is just wrapping up two weeks of training with her new dog.” (By the end of the conference, Sofia received her new pal, a beautiful black lab named Winsome.)

Laura learned raising funds was important, but money alone doesn’t solve the issue.

“Personally, and, for Hope in Focus, the last decade has been a learning experience of all the things that need to come together to pave the way for treatments for ourselves and our children.

Lennon Schleihauf hugs her new doggie. She and other children at the Hope in Focus LCA Family Conference received the plush toys as a gift from Two Blind Brothers. Each dog’s name is embossed in Braille on one of its ears.

“That’s everything from making sure our community has access to genetic testing and is getting diagnosed and not misdiagnosed, which is still an issue in some regions. It includes participating in patient registries and in Natural History studies. It means advocating for policy changes with our legislators, and making sure we are well-informed and educated, and we are all heard.”

Zero to more than 30 Clinical Trials

Ben Shaberman, Vice President of Scientific Communications for the Foundation Fighting Blindness, told the group when he started at the Foundation in 2004, research into blindness consisted of lab work with mice and sometimes dogs, not humans.

Four years later, researchers at Children’s Hospital of Philadelphia began clinical trials for a drug to treat LCA2 RPE65. In 2017, after 12 years and $500 million in research and development, the gene therapy LUXTURNA® received regulatory approval. It is the first treatment in the United States for any inherited disease and the only treatment shown to restore vision in people living with one of the 27 identified forms of LCA.

Today, about three dozen clinical trials involving retinal disease are underway, with 40 biotechnology companies investing in the development of a range of treatment therapies.

“It really is an ecosystem, and you are so much a part of that,” said Ben, who also is an Advisor to Hope in Focus.

He also talked about CRISPR/Cas9, a gene-editing therapy in clinical trials for LCA10 CEP290.

“This was the first ever clinical trial for CRISPR/Cas9, and it was in the retina, and it was for LCA. That clinical trial moved the whole field forward.”

With LCA affecting 8,000 people in the United States and 160,000 globally, Ben told the audience:

“You are moving mountains. Please, please, please, do not underestimate the power that you have to move this forward.”

Hope is Imperative

Years ago, Laura said, someone told her having the word ‘hope’ in our organization’s name was a mistake because hope isn’t a strategy and wouldn’t get us anywhere.

“He’s wrong. Hope is a very powerful thing. And it’s the bedrock of why we founded this organization, and why we still exist. Ten years ago, we didn’t have a single treatment in sight, and we only had hope – hope that someday there just might be a treatment for our child.

“And it was from that hope that this organization was built and continues to grow. There’s not a single person in this room that came here thinking, ‘This is never going to happen, but I’m going to go to Indy anyways.’

“No, everyone is gathered here today because we have some kind of hope in focus – hope to learn something new about this rare disease community, hope to make a meaningful connection with someone else on this journey, hope to bring new information back to organizations in their country, or hope to be the one that brings the next LCA treatment to market.”

*Please see our Hope in Focus website for three more stories detailing sessions from our 2023 LCA Family Conference. Click here to see a video about the conference.

Ready, Set, Go! Hope in Focus 2023 LCA Family Conference Brings Together Rare Retinal Disease Community in Indianapolis

The LCA Family Conference 2023 poster with the date, and times.

People living with LCA, family members, retinal doctors, researchers, advocates, and representatives of the biotechnology and pharmaceutical industries converge in the racing capital of the world this weekend, when Hope in Focus presents its third LCA Family Conference.

A global advocacy organization helping those affected by blindness, Hope in Focus connects families living with Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs) through its Family Connections program and through events such as this conference at the Omni Severin Hotel in downtown Indianapolis from Friday, June 23, to Saturday, June 24.

The gathering creates an ideal environment for creating opportunities for thoughtful and interactive exchanges of knowledge, ideas, and viewpoints in sessions focusing on research, future treatments, advocacy, people sharing their stories, and making connections with people traveling similar journeys.

The conference is sponsored by Spark Therapeutics, Foundation Fighting Blindness, MeiraGTx, Janssen, Atsena Therapeutics, Ocugen, and Kiora Pharmaceuticals. We offer special thanks to Eighty Six Media, Indiana School for the Blind and Visually Impaired, Scott D. Allison, OD, MBA, Lori St. Arnaud, and Lee St. Arnaud.

Courtney Coates, Director of Outreach and Development for Hope in Focus, and Laura Manfre, Board Chair and Co-Founder of our organization, kick off the event by sharing the ways in which we are supporting the LCA and rare IRD community.

Our first panel is about Advocating for Treatments, moderated by Jonathan Stokes, AbbVie’s Senior Director of Patient-Centered Outcomes Research. Panelists are:

* Jacose Bell, Senior Patient Advocacy Lead at Spark Therapeutics

* Wiley A. Chambers, MD, Supervisory Medical Officer of New Drugs, Center for Drug Evaluation at the U.S. Food and Drug Administration

* Jill Dolgin, PharmD, Executive Director of Global Patient Advocacy & Scientific Engagement at Beacon Therapeutics

* Laura Manfre, Co-Founder and Board of Directors’ Chair

* Emily Place, MS LCGC, Senior Genetic Counselor and Manager of Genetics and Genetic Counseling at Mass Eye and Ear

***

A second panel explores Living with LCA, moderated by Lee St. Arnaud, a father of two teen-agers living with LCA. Panelists are:

* Beth Borysewicz, Educational Consultant, State of Connecticut Department of Aging and Disability Services with the Bureau of Education Services for the Blind

* Mohamed Farid, Founder and CEO, MFK Continuity

* Tami Morehouse, LCA research pioneer, who lives with LCA2 RPE65 and volunteered for the first clinical trial for gene therapy

* Patrick St. Arnaud, who lives with LCA17 IQCB1/NPHP5 and is a high school senior

* Mirielle St. Arnaud, who lives with LCA17 IQCB1/NPHP5 and is a high school junior

***

A session will be held on LCA Drug Development by our partners at the Foundation Fighting Blindness. The speakers are Chad R. Jackson, PhD, Senior Director of the Foundation’s Preclinical Translational Research Program, and Ben Shaberman, Foundation Vice President of Science Communications.

***

Another panel will discuss Gene Agnostic Therapies, moderated by Chad R. Jackson, PhD, with panelists:

* Huma Qamar, MD, MPH, CMI, Head of Clinical Development and Medical Affairs at Ocugen

* Eric Daniels, MD, Chief Development Officer at Kiora Pharmaceuticals

* Ben Shaberman, Vice President of Science Communications at Foundation Fighting Blindness

***

The last panel will discuss Gene Therapies for LCA, moderated by Ben Shaberman of the Foundation. Panelists are:

*Shannon E. Boye, Founder and Director and Acting Chief Science Officer at Atsena Therapeutics

* Ash Jayagopal, PhD, Chief Scientific Officer, Opus Genetics

* Thomas Mendel, MD, PhD, Assistant Professor of Ophthalmology, and Vitreoretinal Surgeon, Havener Eye Institute, Department of Ophthalmology & Visual Sciences of The Ohio State University

* Bikash R. Pattnaik, PhD, Professor, University of Wisconsin-Madison

***

Hope in Focus is dedicated to generating awareness, raising funds for research, and providing support, education, and outreach to the LCA and rare inherited retinal disease community.

We look forward to seeing you at our LCA Family Conference!

Noah’s Journey: Living and thriving with LCA9 NMNAT1

Five-year-old Noah Johnson lives in a special place where he can see rockets shoot into the air at night.

“I can see,” he yells to his mom, Stephanie. “I can see the rocket!”

One of the big joys of living in Melbourne on Florida’s Space Coast is witnessing dramatic liftoffs from nearby Cape Canaveral, especially when it’s dark.

“It’s so heartwarming because he can see what everyone else can see,” his mom said.

Noah also can see colors, faces, and at night, he can see the moon.

During the day, he can hear the booming roar of the magnificent engines, but unlike in darkness, he can’t see the spacecraft soar into the great beyond.

Noah sitting with a black shirt and grey shorts. — Noah

Stephanie and her husband, Brian, noticed in 2018 the rapid, side-to-side movements in the eyes of their 4-month-old. Stephanie now knows that the eye-movement condition, known as nystagmus, presents as a symptom of the rare inherited retinal disease Leber congenital amaurosis, known as LCA.

After following up with a pediatric ophthalmologist, the doctor asked Stephanie’s other children if they could leave the room, while she wondered, “What is going on?”

The family left the office with many questions and only one vague answer: Something was extremely concerning about Noah’s retina.

Getting a confirmed genetic diagnosis

Noah soon underwent what his mom described as a “horrible and kind of brutal” eye exam. She wants doctors and parents to understand the difficulty of getting an infant to sit still and open his eyes.

The extensive exam used eye hooks to expose his eyeball.

“They put the ultrasound gel directly on the eyeball. I am so thankful as a parent that we’re beyond that, as it was extremely difficult to watch and for him to experience.

“Everyone has their own journey. If I had known there were better imaging options when he got older, I would have asked more questions and inquired if we could wait. The imaging is different and a 2-year-old has the ability to sit and look straight.”

The couple declined an electroretinography (ERG) test that detects abnormalities in retinal function. Even if the earlier testing had gone more smoothly, they didn’t want the doctors to perform the test.

“We were not comfortable putting him under anesthesia,” Stephanie said. “It would give a disease diagnosis but would not confirm the type of LCA. For us we decided against it, for now.”

Noah with his graduation cap on holding his certificate with a fun background saying "Preschool graduate!". — Noah graduating from Pre-K

Noah’s parents instead moved forward with genetic testing, receiving their son’s diagnosis of LCA and a confirmed genetic diagnosis of LCA9 NMNAT1.

“I can tell you this, when we first got Noah’s diagnosis, it was extremely emotionally hard, and it took a whole season of trying to come to grips with it,” she said. “What does it look like? We don’t wear glasses, no one in our family wears glasses or has anything wrong with their vision. It came completely out of nowhere; it was a bit of a shock.

“We just dove deep into our faith, and we had so much of a peace about it. We just cried to God about it. That sustained us through that time of all these things going through your head about what he’ll ever be able to do and whether vision is the only issue.

“There’s a still a unique peace about it that we carry to this day.”

Looking forward to the 2023 LCA Family Conference

The mother of five, working at home full-time as a health insurance account manager, and her husband, who is an occupational therapist with the Veterans Administration, sought out as many people and organizations as possible to find services, to understand LCA, and to learn about retinal disease research.

“I was thinking of people to walk this journey with because it’s an extremely rare diagnosis,” Stephanie said. “I was trying to find other people who have walked through this and are now adults.”

She also attended the 2019 Hope in Focus LCA Family Conference in Philadelphia, where she connected with other families living with LCA and researchers working on treatments for the disease.

And she’s planning to attend Hope in Focus’ third LCA Family Conference this week from June 23-24, 2023.

The Johnson Family: (L) Stephanie (mom) holding Addisyn; Faith (behind Addisyn); Emma, Brian (dad), Noah, and Ryan — The Johnson Family

“I think the LCA conference is so vital. It was a great experience, and I’m looking forward to it even more this year.

“We’ve been at this much longer. We know more, we know what to ask. With Noah going into kindergarten, it’s important to connect with families and talk about how their children went through kindergarten.”

While she’s excited about advances in LCA research that could help Noah, she worries about the effectiveness and risks of trying new therapies.

“The progress made in just the past five years is amazing, and we are optimistic for further advancements, especially for NMNAT1.”

**Biotech to advance NMNAT1 gene therapy research**

Stephanie finds comfort knowing Noah’s form of LCA is among three in the scope of research advancement by Opus Genetics, a biotech created through the Foundation Fighting Blindness’ Retinal Degeneration Fund (RD Fund) to invest in projects in, or advancing toward, early-stage clinical trials.

Ben Yerxa, PhD, Chief Executive Officer of Opus, characterized the company as a first-of-its-kind model for patient-focused development.

“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.”

Opus’ lead program addresses mutations in the LCA5 gene encoding the lebercilin protein. The next one focuses on LCA13 RDH12, caused by mutations in the retinal dehydrogenase gene.

The company’s third program targets LCA9 NMNAT1, the gene mutation affecting Noah’s vision.

Stephanie met the Foundation’s Ben Shaberman and Ben Yerxa at the 2019 conference when he served as Foundation’s CEO.

“It just feels so exciting that he is leading Opus. He is a wealth of knowledge for the blind community and has been essential in raising money for research, as money is such a major part of moving this research forward.”

Black and white photo of Noah standing — Noah

Onward to kindergarten

Doctors think Noah’s vision is 20/200, with little central vision and more peripheral vision. Considered legally blind, Noah navigates well, with most people not even knowing he has vision loss.

“I’m just excited, but nervous, about him going into the school this fall, just because I’ve never walked this journey with a school-aged child.”

Stephanie and Brian look forward to meeting and talking with other families living with LCA to gain insight into their son’s progress.

For now, though, Noah continues enjoying his favorite food – pepperoni pizza – and his favorite things: Toy Story movie’s Buzz Lightyear, monster trucks, and, at night: the rockets and the moon.

Let’s Chat About … RARE-X with Karmen Trzupek

Through global data sharing and analysis, the nonprofit RARE-X (the research arm of Global Genes) is working to accelerate treatments for rare diseases, including Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs).

Hope in Focus featured Karmen Trzupek, RARE-X’s Senior Director of Scientific Programs, in its webinar episode “Let’s Chat About…RARE-X.’ Our Director of Outreach and Development Courtney Coates discussed with Karmen RARE-X’s mission and goals, and its recent merger with Global Genes. The March 7, 2023, session can be viewed here.

“Let’s Chat About…” is our free webinar series bringing together researchers, advocates, industry leaders, and people living with LCA and other rare IRDs for conversations important to the rare retinal disease community.

RARE-X and its founding

Nicole Boice founded Global Genes to support patients, families, and patient advocacy groups dedicated to rare diseases. At Global Genes, Nicole and others recognized a tremendous need to solve data collection and sharing problems for patient communities affected by rare diseases, and founded RARE-X to address those critical data issues

Rare disease patients’ data often is collected somewhere and sits privately in a silo where it is inaccessible to others. Or, the patient community actively manages the data in a format precious to a particular researcher, but unhelpful to others. Or, the data doesn’t exist, as is the case with many rare diseases.

RARE-X began addressing these issues through its data collection platform that enables rare disease communities to start gathering data in a highly structured and streamlined way that aligns with existing research philosophies.

“We work very hard at RARE-X to make sure that every single question asked of patients and families is a valid data point,” Karmen said. “Then we also share that data. With patient permission, all the data collected on the platform gets migrated to a data-analysis platform, and any qualified researcher can access that data.”

Collecting the data

“When someone first comes onto the RARE-X platform and starts entering data, it will ask them for their self-reported diagnosis. Do you have a genetic test? It asks about symptoms and the progression of those symptoms over time.

“We have people upload a copy of their genetic test results for the genetic testing data. Then we have a genetic curation team that reviews those, pulls out that data and makes sure that that data is in discrete data points. That’s useful to researchers because a researcher coming onto the platform does not want to pour through a whole bunch of PDFs and sometimes pictures from somebody’s phone of their test results, so we curate all of that data and make sure that that’s available on the research portal.”

Collaborations through RARE-X

Karmen develops programming and strategic collaborations to ensure the company makes the best use of the data that patients and families entrust to them.

In one program, she’s managing an “Open Science Data Challenge” with data from about 30 patient advocacy groups in the pediatric neurodevelopmental space, in collaboration with families of children with disorders causing seizures and global developmental delays.

“We are pulling the data and aligning it with other partner data, and then making it widely available to an extensive research community under a challenging environment, like a hackathon, to try to generate valuable insights and create research proposals for grants.”

Karmen also is looking at how RARE-X develops partnerships for additional data sources and uses of the data that circle back to benefit the patient community. Other groups on the platform include some adult-onset neurodegenerative disorders and some inherited retinal disorders.

“Usher syndrome, for example, that community is actively collecting data on the platform. And then other related inherited ocular conditions that aren’t retinal but share overlapping issues and needs, like Leber hereditary optic neuropathy, are collecting data.”

The company also plans to make digital optical coherence tomography (OCT) data available side-by-side with patient reported data.

“Those images are proprietary to the software and the hardware used. Multiple companies make OCTs, and we’re working with an artificial intelligence group that has developed ways to bring that data together and make it cross-comparative.”

RARE-X plans future LCA community data collection

“The platform has been live for about a year and a half, and we are very much building this plane as we fly it,” she said. “We’re working in the vision consortium to ensure that we’re adding the right kinds of surveys and patient-reported outcome measures to the platform that are most useful to this patient community.

“We’re continuing to talk with Hope in Focus and other groups within the LCA family of diseases. As soon as we start to have some more vision-specific surveys, we’ll begin collecting data pretty actively.”

From genetic counselor to RARE-X’s mission

Karmen’s career began as a genetic counselor in inherited retinal diseases. She worked at the C a sey Eye Institute and then InformedDNA, where she developed ways to share the experience and information received by patients and families seen at a major academic research center with patients and families unable to physically get to a major center. Telemedicine and collaborations and partnerships with local retinal specialists accomplished much of that.

But she realized a much greater need overall for rare disease information sharing and for funding. Through the Usher Syndrome Coalition, Karmen met Nicole and Charlene, the RARE-X founders.

“I loved the mission and that they’re enabling even the smallest patient groups to start becoming very actively involved in clinical research,” she said.

“They are flipping that paradigm where a patient community doesn’t have to wait for a clinical trial or a natural history study for their data to be valuable. But flipping where the patient communities drive the research agenda and begin to say, ‘look, we have the data, and we have started to de-risk this disease as a disease that would be valuable to pharma to invest in.’ I love that paradigm shift. I love getting to be part of that.”

Merger benefits the rare disease community

“Coming together and joining Global Genes helps the entire journey of the patient advocate. If you think about a rare disease patient or parent, you start on your diagnostic journey searching for the diagnosis, right?

“You get that diagnosis, and maybe a patient foundation or community already exists. Maybe not, if it’s an ultra-rare disease. Those patients and families going through that have lots of needs. Those questions might include: Where do I go from here? How do I best support my child in the school system?

“The patient-advocacy journey is something that Global Genes, for a long time, has been very involved in. RARE-X has been developing this platform and developing partnerships to use this data, and now we can provide an extension of that patient advocate journey.

“So much of what both Global Genes and RARE-X have been doing is related to how we educate and support patient advocates in becoming more active participants in research and helping to drive that research agenda. I think there was a lot of overlap that was beginning to develop there. It made sense to merge.”

The future for RARE-X

The U.S. Food and Drug Administration recently approved therapy for a rare neurologic disorder, and for the first time, it accepted

data from an ongoing natural history study as essentially a control arm.

“That brought up a lot of excitement and questions around patient-generated data because the patient community drove that natural history study. RARE-X and Global Genes have an opportunity to be part of this story and its evolution,” Karmen said.

“Now I am not suggesting that clinical data and traditional natural history studies will be replaced. There’s so much value in those studies, but we also know that they only ever capture a small percentage of the patient community who can travel.

“How can we make that kind of research more broadly available to a much larger population of patients and find something that’s a little bit more hybrid? That is a massive part of where I see us going in the next five years.”