ProQR Completes Enrollment for Next Phase of RNA Therapy for LCA10-CEP290

ProQR Therapeutics reached an important milestone by completing enrollment in the next pivotal phase of clinical trials of sepofarsen, a developing RNA therapy for treating LCA10, a form of Leber congenital amaurosis (LCA) with a mutation in the CEP290 gene.

The biotechnology company based in Boston and in Leiden, The Netherlands, announced earlier this month that it finished enrollment in its Phase 2/3 Illuminate study of sepofarsen for treatment of LCA10 due to the p.Cys998X mutation in the CEP290 gene.

LCA10 is a severe retinal dystrophy, causing blindness or severe visual impairment at birth or during the first months of life. The mutation affects about 2,000 people in the Western world.

Sepofarsen is an antisense oligonucleotide (AON) that works like “genetic tape” to fix the mutation. The therapy is unlike gene replacement therapies in which whole genes are delivered to replace defective copies.

The drug aims to repair the genetic defect that causes the disease in the ribonucleic acid (RNA). The mutation leads to an aberrant splicing of a person’s messenger RNA (mRNA) and leads to a non-functional CEP290 protein. Sepofarsen is designed to enable normal splicing, resulting in subsequent production of functional CEP290 protein.

Recruiting patients for clinical trials represents one of the biggest challenges in getting studies underway. The COVID-19 pandemic and concerns about spreading the virus presented an unprecedented challenge in and of itself. Pharmaceutical companies also have steered their focus from studies across the board as they raced toward developing and rolling out worldwide virus vaccines.

Finding the required 33 LCA10 individuals for the Illuminate trial in a subset of a people with a rare condition was exceptionally challenging, and ProQR exceeded that requirement by enrolling 36 participants.

During the Phase 2/3 study, the 36 patients, ages 8 and older, are set to receive sepofarsen either in a dose expected to be used once the drug gains approval or a lower dose or a placebo. The 12-month clinical trial is intended to support an application for marketing approval of sepofarsen. The study is being conducted in the United States, Canada, Brazil, The Netherlands, Belgium, France, Italy, Germany, and the United Kingdom.

The drug is administered through intravitreal injections in the eye. It is also a platform for use as transformative therapies for treating Usher syndrome and retinitis pigmentosa (RP).

Top-line results in early 2020 from the Phase 1/2 clinical trial of sepofarsen in 11 children and adults revealed that 60 percent of patients had improvements in visual acuity and navigating a mobility course. The study, carried out in the United States and Belgium, also netted a super responder, a person who responded particularly well to the treatment.

Laura Manfre, chair and co-founder of Hope in Focus (formally Sofia Sees Hope), said that as the parent of a child with an LCA diagnosis, she was told there was nothing that could be done and that her family needed to accept that their daughter would one day be blind.

“Now, in early clinical testing we have seen the potential for sepofarsen to make a significant difference for patients with LCA10 due to a mutation in the CEP290 gene,” she said. “We see hope for individuals living with this disease. We look forward to learning about the results of the Illuminate trial and continuing to work with ProQR as they advance their pipeline of RNA therapies to potentially help children, adults, and families who are affected by blindness caused by LCA and other rare inherited retinal diseases.”

Aniz Girach, MD, ProQR’s chief medical officer, said in a statement that the company was pleased to have completed enrollment of the Illuminate trial of sepofarsen.

“This marks an important milestone for ProQR, as well as for the LCA10 and broader inherited retinal disease community,” Girach said. “In surpassing our enrollment target, we were able to accommodate the broad interest to participate in the trial. This speaks to the fact that there are currently no approved treatments for patients with LCA10.

“If approved, sepofarsen has the potential to be the first therapy to address this high unmet medical need for patients who would otherwise face blindness, he said.

“We are grateful to those who have supported our efforts in bringing this trial forward, including our investigators, patients, and caregivers. We look forward to sharing the top-line results in the first half of 2022.”

Reflecting on the Trajectory of IRD Research

When I joined the Foundation Fighting Blindness as a science writer in 2004, I really didn’t know what I was getting into. I knew nothing about the retina, let alone the complex and diverse world of rare inherited retinal diseases (IRDs) that includes Leber congenital amaurosis (LCA). But the research for treatments was cutting-edge and compelling, so I was excited to dive in and learn.

My early assignments were writing about laboratory studies coming out of academic labs. There were virtually no companies in the IRD space and only one or two clinical trials underway for emerging therapies. But there were a lot of studies of genetically engineered mice and rat models of IRDs for gaining a better understanding of disease pathways and testing potential treatments.

Truth be told, I often wondered if and when rodent-tested therapies were really going to make it into human studies and out to the people losing vision. But the scientists conducting the research were mind-blowingly smart and innovative, so I figured they knew what the heck they were doing. With a master’s degree in poetry, who was I to judge?

Fast forward about four years: I was in my hotel room in Fort Lauderdale – there for the annual Association for Research in Vision and Ophthalmology conference – when my manager called and told me three research groups just reported vision improvements in young adults treated with RPE65 gene therapies in Phase 1/2 clinical trials. That was the breakthrough we’d all been waiting for.

People, rather than animals, with severe vision loss were now seeing significantly better. It was the first time an IRD treatment had worked in humans. I will never forget the headline for the article I immediately wrote: “Now They See.” (Note: One of those RPE65 gene therapies later became LUXTURNA®, the first FDA-approved treatment for the eye or an inherited condition.)

After many years of painstaking work, our hope for treatments and cures had finally begun evolving into promise.

There have been several other aha! moments in the ensuing years, but I distinctly recall cathartic encounters at the 2019 American Society of Retinal Specialists in Chicago. As I perused the snack table during breaks (the accomplished snacking professional that I am), several representatives from biotechs developing IRD therapies – companies I’d never even heard of – came up to introduce themselves to me and tell me about their emerging IRD treatments. They didn’t know me or my role, nor had I previously known them; they were just eager to connect with someone from the Foundation Fighting Blindness to get on our radar screen.

I realized then I couldn’t keep track of all the companies (dozens) focused on IRDs and clinical trials (40-plus) underway for potential IRD treatments. But being overwhelmed felt incredibly good, and it meant more good news likely was on the horizon for saving and restoring vision.

While mouse studies are as critical as ever, I can’t remember the last time I wrote an article about one. That’s because most of my writing is now dedicated to reporting on advances, including encouraging vision improvements, being made in human studies.

Make no mistake: Much more work needs to be done before we eradicate the myriad IRDs affecting millions of people across the globe. And, of course, we cannot get more therapies across the finish line fast enough. But when I look at how incredibly far we’ve come since those early days of mice and rats, I have no doubt we are well on our way to breaking many more ribbons soon.

Nearly Three Years Later, LUXTURNA®™ Treatments Continue to See Success

Since its launch in March 2018, breakthrough gene therapy LUXTURNA®™ continues to be successful in helping improve vision in people with inherited retinal disease due to mutations in both copies of the RPE65 gene and viable retinal cells as determined by a healthcare professional. The therapy treats LCA2, known as LCA/RPE65, one of more than 25 forms of Leber congenital amaurosis.

The drug – developed by Spark Therapeutics and a team of retinal research superstars that included Dr. Katherine A. High and Dr. Jean Bennett – came to fruition after 12 years of research and millions of dollars in investment.

Spark Therapeutics could not comment on the number of people who have received the gene therapy, but spokesman Kevin Giordano recently said the company has shipped well over 200 vials of the therapy since the U.S. Food & Drug Administration approval in December 2017. One vial of the drug treats one eye.

Trained retinal surgeons at one of the 10 eligible treatment centers in the United States deliver the gene therapy to the back of the eye by subretinal injection using a needle the size of an eyelash; about a week or so later, the patient undergoes the procedure in the other eye.

Read: 10 US Centers Offering Treatment

“Spark Therapeutics is thrilled patients continue to benefit from LUXTURNA (voretigene neparvovec-ryzl),” Giordano, Spark’s External and Product Communications Lead, said. “A gene therapy is a major milestone, not only for those of us at Spark, but also for the patient community and broader gene therapy field.”

The cost of the drug – $425,000 for each eye – initially caused anxiety among patient families, but Giordano had good news about insurance coverage.

“Payer coverage has exceeded expectations, and to our knowledge no treatment-eligible patient has been denied treatment due to their insurance coverage,” he said.

LUXTURNA also is being used beyond this country through license and supply agreements with Novartis, which has the rights to commercialize the drug in Europe and all other markets outside the United States. Spark manufactures and supplies the gene therapy to Novartis, according to Giordano.

Also, results from ongoing studies continue to support the drug’s safety profile and efficacy.

“In 2019, Spark presented four-year durability data from the LUXTURNA Phase 3 clinical trial,” Giordano said.

Read: LUXTURNA safety information

For privacy reasons, Spark Therapeutics cannot share patient results.

But we can – at least a couple of them because they came from patients and families sharing their stories with us.

For Hannah, ‘Hope Realized’

Hannah Reif, daughter of Amy and Chris Reif of Maple Glen, PA, underwent LUXTURNA gene therapy in July 2018. Dr. Albert M. Maguire, who is married to researcher Dr. Bennett, performed Hannah’s surgery at Children’s Hospital of Philadelphia (CHOP).

Hannah with a big smile, wearing a light blue green coat and holding a drink — Hannah Reif

“We closely watched the clinical trials and the FDA approval process for seven years, starting when Hannah was diagnosed with LCA/RPE65 at just a few months of age,” Amy said. “Seven years of hope.

“Two years out from Hannah’s surgery, I can say we feel grateful and fortunate that she was treated with LUXTURNA. No regrets. LUXTURNA was hope realized. It delivered what it promised.”

She said what that has meant for Hannah has been nothing short of life changing.

“It has given her more independence, which has been wonderful for her self-confidence. It has given her the ability to see what she couldn’t before.”

Since the surgery, Hannah’s vision in dim lighting and her visual acuity improved. She is now 9 and just finished third grade.

Sometimes, her mom said, it’s the little things that are the most amazing.

“A year after the surgery, she was about to eat hot oatmeal and said, ‘Hey, I see steam. Hey, I can see that,’ ” Amy said.

“There are still things that pop up that she’s seen for the first time, like when she said, ‘Mom, did you know there’s a pattern on this toy?’ It’s fun to see her discovering.”

Amy said she and her family will be forever grateful to Dr. Bennett.

“There has been a lot of talk about heroes recently and Dr. Bennett is our hero. We are grateful for this groundbreaking treatment that she developed, that has been life-changing, not only for our daughter, but also for the sons and daughters and loved ones of so many others as well.”

‘His Vision Changed Everything’

Creed Pettit, one of the first recipients LUXTURNA, received the gene therapy at age 9 in March 2018. Dr. Audina M. Berracol performed the surgery at Bascom Palmer Eye Institute in Miami, Fla.

His mom, Sarah St. Pierre Schroeder, told us that her now-11-year-old is doing amazing and only occasionally has issues with dim lights, “but nothing like before.”

Their days in Mount Dora, Fla., have changed in a major way.

“He still starts his day with his trusty smoothie and waffle, but after that, Creed wants to create new pranks (today was putting ice in the tub). He said it was nice and warm so I could soak my feet.”

Creed in blue glasses, holding his Uno Cards — Creed Pettit

Creed now loves to play board games – Trouble, Sorry, Battleship and Uno.

“His vision has changed everything. He can manipulate small objects, he is using pointer fingers, and loves trying to roll his eyes in the mirror.”

Creed still likes to draw, and he loves riding and popping wheelies on his bike named Carlitos. He also likes to talk.

“Talking more is an understatement! Sunup to sundown, he is talking. He has also learned how fun it is to use his imagination, something he never did before. He creates awesome stories during this time. He is so much more independent; I have to remind myself of that often.”

At first, she and her husband, Chad, could see that Creed’s vision improved some, but once he became confident about his gene replacement, they noticed him finding toys and games.

“He was suddenly enjoying things he didn’t before. He now expresses when he can’t see. Yesterday it rained all day, I kept waiting for him to tell me it was too dark inside, but he was fine. He just started doing staring contests. I love looking at his eyes during the contest.”

Sarah said she is incredibly grateful.

“Creed’s surgery is something we still thank God, St. Raphael, St. Lucy and Sister Miriam Teresa, for every night.”

Like many kids across the country, Creed finished school at home because of the coronavirus pandemic. He graduated from fifth grade and thought because he finished school at home, he wouldn’t have to wear the graduation cap.

“But I was not going to let that slide,” his mom said. “I made one and took pictures.”

Anxiety, and a Friend to Call On

Throughout his journey, though, Creed felt anxious, something Sarah had learned that might happen when, before Creed’s surgery, she talked with Tami Morehouse, a LUXTURNA clinical trial participant at age 44.

Tami, a Sofia Sees Hope Ambassador, tries to calm fears and advises potential gene therapy patients and their parents that even though undergoing the surgery has the potential to do such good by improving vision, they should think about their expectations, especially with children.

“We are comfortable in our own zone; give us a little bit of change and it can throw us off,” Tami said.

Sarah understands.

“He started to have a lot of anxiety. He had a hard time sleeping. I feel everything changed so fast that he was overwhelmed, but we have worked hard on getting past that.”

Sarah and her family are in a great place now. But after they were home from the hospital in Miami and settled into their routine, she said she became very emotional.

“All the tears I had held in for nine years started to come out. I felt I no longer had a purpose; I was so used to staying busy. I did not know who I was supposed to be.”

She got some help and realized she still was needed because people need her help learning about and understanding this groundbreaking gene therapy.

“I still find myself shocked over how this has changed Creed’s life and so many other lives.”

Clinical Trials and Emerging Research Show Promise for LCA Treatments

Forty clinical trials and a lot of pre-clinical research into LCA treatments show promising pathways to discovering the next LUXTURNA®, according to Shannon Boye, PhD, the opening speaker for the Virtual VISIONS 2020 conference, presented earlier this summer by the Foundation Fighting Blindness.

The breakthrough drug developed by Spark Therapeutics marked a milestone in the history of genetic research as the first gene therapy in the United States for any inherited disease and as the first to treat one of the more than 25 forms of Leber congenital amaurosis (LCA).

Shannon Boye, PhD in a lab coat — Shannon Boye, PhD

Boye, along with Foundation Chairman of the Board David Brint and Foundation Chief Executive Officer Benjamin Yerxa PhD, kicked off the three-day, first-time virtual conference, the Foundation’s major annual gathering. Rather than convening in person, the event’s speakers, exhibitors and more than 1,600 attendees participated through an online app, due to concerns surrounding the coronavirus pandemic.

Brint said that the 40 clinical trials and more emerging treatments for various IRDs span the disease profile.

“No matter what your disease is, these hopefully will be able to restore vision,” Brint said. “In the next 10 years, we have an opportunity to bring many more vision-saving treatments into and through the pipeline and across the finish line.”

Yerxa said the topic of genetic therapies would be good to lead off with because of the sheer variety of innovative programs and approaches to each therapeutic challenge.

“There’s essentially a revolution happening right now in personalized medicine and genetic therapies in general,” Yerxa said.

Boye, an assistant professor in the Department of Ophthalmology at the University of Florida, addressed the audience in the beginning session called: “Mission Possible! What’s Next?”

She discussed three major strategies in treating LCA and other IRDs: Gene supplementation or gene replacement therapy, RNA therapeutics and gene editing.

Boye set up an analogy to better understand the complexities of these strategies, saying we all have little letters in our bodies called DNA. Subunits of those letters – that DNA – are genes. RNA carry the instructions from DNA for making proteins, the building blocks of life.

“They act alone or in concert with a bunch of other proteins to perform essential functions.”

Continuing her letters analogy, Boye said, imagine a friend texts you: ‘Please take out the dog.’ You get that message and perform that function because letters combined correctly to tell you to take the dog out.

If only the word ‘Please’ appears on your phone screen, you don’t take the dog out.

Or, if the ‘d’ is pushed and an ‘l’ comes out, sending the message, ‘Please take the log out,’ “you then have a mess to clean up,” she quipped.

In the first strategy of gene supplementation or gene replacement, the right protein needs to be expressed in the patient’s retina.

The letters need to be correctly sequenced to generate a coherent message, in this case, telling a protein to perform an important function. Any break in that cascade of events can cause visual impairment.

The gene replacement therapy LUXTURNA is a human-engineered virus containing copies of the corrective gene that doctors deliver through a subretinal injection so the cells can make the originally missing protein.

“You deliver the right letters that make the right message and the right protein,” she said. “That’s a pretty simple concept. That’s LUXTURNA.”

Developed to improve vision in people with LCA2* caused by a mutation in the RPE65 gene, LUXTURNA received Food and Drug Administration approval for use in humans in December 2017.

One area of Boye’s research as Associate Division Chief of Cellular and Molecular Therapeutics is entering into a Phase 1/2 clinical trial, applying the same premise for mutations in the GUCY2D gene that causes LCA1.

“It’s early,” she said. “But this is an example of another perhaps next LUXTURNA being right around the corner.”

She cited similar research moving forward on other IRDs, including Retinitis Pigmentosa (RP), Choroideremia, and Bardet Biedl Syndrome (BBS).

The second strategy is a form of RNA therapeutics that uses antisense oligonucleotides (AONs) – short, single-stranded DNA molecules that interact with messenger RNA to correct translation of a targeted gene. Think of an AON as an autocorrect feature that binds to the ‘l’ in log and changes to a ‘d’ for dog.

Promising pre-clinical work now in Phase 2/3 for CEP290 or LCA10 also is coming out of Rob Collin’s research group in The Netherlands, Boye said.

Another AON program underway addresses a form of Usher Syndrome.

The third strategy – the newest and most exciting – is gene editing. A guide RNA is used to drag a special enzyme to a region in the DNA that contains the mutation, and the enzyme cuts the DNA, like molecular scissors.

Researchers are exploring a host of gene editing variations, including cutting out a specific area of DNA and replacing it with the right letters to make a coherent message. The lab work has created paths to address a range of IRDs, including CEP290, Usher Syndrome, RP, Stargardt Disease and Choroidermia.

“There’s an absolute exponential increase in the therapies that are being developed,” she said.

These strategies are not limited to the disease conditions under discussion and can be more widely applied to a number of genes and conditions.

Addressing those who do not have RPE65 or LCA2 for which a treatment exists, Boye said, with all of this research in progress, “that one day, there’s going to be a LUXTURNA for your inherited retinal disease, too.”

Living with LCA: Finding Her ‘Light’ In the Kitchen

A recipe for addiction recovery transformed Orly Shamir’s life, and now it’s about to change her future.

Orly, who’s name in Hebrew means “My Light,” lives with LCA4, a form of Leber congenital amaurosis caused by a mutation in her AIPL1 gene.

The 52-year-old Canadian, newly transplanted to southeastern Florida, takes her Hebrew name literally.

“I am light, and I am vision,” she said. “I want to offer everything I have for others to realize their perfect light and vision is possible.”

As a child she had enough vision to read large print, but in her 20s, Orly’s sight deteriorated to minimal light perception and shadows. In 2014, she was part of a clinical trial in Canada for the Argus Retinal Prosthesis System (Argus II). The Argus II, known as the bionic eye, stimulates the eye with electrodes to transmit visual information captured by a video camera to the patient’s brain. You can read about her experience in the trial here.

“Still, I have true 20/20 vision,” she said. “My blindness forces a mindful clarity through all my other senses and that enriches everything from my cooking and healing, to my service to others.”

Along her journey through the darkness of an opiate addiction, she rediscovered her mother’s traditional Moroccan fish dish, served as part of each Friday’s sabbath dinner.

Little did she know the importance this recipe would have to her survival.

From 1999, after having her third child, until 2012, she said, “My opiate addiction took a huge chunk of my life away because it

Orly and Amit nicely dressed at Dinner in the Dark 2019 — Orly Shamir and her husband Amit (and guide dog Regan at the 2019 Dinner in the Dark to benefit Hope in Focus (formally Sofia Sees Hope).

was a fight. That’s why I want to give back and give light to the darkness.”

It began with chronic pain and prescriptions for Percocet and Oxycontin that offered relief and a false sense of well-being. Domestic abuse led to living in a shelter with her children. Orly finally realized she needed to get off the pills, but she could not.

“It was the beginning of torture for several years. That’s why we have an epidemic with opiates. It takes a lot of strength and support, and I tried three times over a four-year period. It takes everything out of you to get to the other end and never look back.”

Childhood memories of simmering aromas of lemons, parsley, cilantro, peppers, tomatoes and all the spices helped get her to the other side.

She tweaked her mother’s recipe during one of her mom’s visits from Montreal to Orly’s home in Toronto. When her don’t-you-dare-mess-with-ingredients mom left the kitchen, she took the opportunity, with guilt-laced excitement, to add a few more to the pot.

“Voila, my specialty Moroccan Salmon, the champion of my life was born! At dinner my mom raved about her wonderful fish, and all I did was smile while my soul did a happy dance.”

Years later her addiction took its toll with memory loss and less ability to perform skills. She realized that improving her cognition could be accomplished several ways, including by eating healthy food, especially fish like salmon with lots of omega-3s.

It’s fatty, versatile and widely available, which is why Orly says her dish is champion food for anyone on any recovery journey, whether from illness, addiction or the blues.

“Without knowing it, this spiritually comforting food became physical healing food.”

Blind Ambition

Orly is a gifted chef, a title-holding athlete (Italian and Canadian dragon-boat racing!), a financial analyst fluent in French and a motivational speaker. She has two sons and a transgender daughter, all in their 20s living in Canada. Orly, her husband of 12 years, Amit, and her guide dog, a 6-year-old Black Lab named Regan, live in Hollywood, Fla.

She just graduated from a Florida culinary school with her sights set on developing a YouTube cooking series and a recipe app.

To help finance her project, she applied in January for the Holman Pri z e for Blind Ambition by making a 90-second video about her project of combining culinary and cooking expertise with her inspirational recovery story.

“Do you know blind people are 40 percent more likely to develop addictions?” she tells viewers in her video. “And did you know proper nutrition is key to recovery? … Although I’ve been legally blind my whole life, I lost my soul’s true vision through opioid addiction and poor health.”

Orly sitting next to her black lab — Orly Shamir with her guide dog Regan.

Orly is turning her recovery story into a series of videos demonstrating healthy, delicious culinary delights, an accessible-to-all recipe app, and input from guest experts to help heal through the art of cooking.

She fashioned her simple and nutritious recovery recipes by using pronounceable ingredients, healthy fats, nuts and seeds and the like.

“It gives us more mental and physical strength because we start to feel better. We’re not as sluggish.”

Orly learned in March that she is one of 39 semi-finalists for the Holman Prize, selected from 109 applicants worldwide. Three winners will be selected in May.

The Holman Prize for Blind Ambition is annually awarded to three blind individuals to carry out a dream project to push limits and change perceptions about blindness around the world. The prize honors James Holman, a Victorian-era adventurer and author who became the first blind person to circumnavigate the globe; he also holds the distinction of being the most prolific traveler in history, sighted or not, prior to the invention of modern transportation.

Each Holman Prize winner receives up to $25,000 to fund a project or an adventure that will make an impact. The contest is sponsored by LightHouse for the Blind and Visually Impaired in San Francisco. The organization launched the prize concept to support the emerging adventurousness and can-do spirit of blind and low-vision people worldwide.

LightHouse CEO Bryan Bashin said the Holman Prize is not meant to save the world nor to congratulate someone for leaving the house. It is meant to change perceptions about what blind people can do.

“This prize will spark unanticipated accomplishments in the blindness community. You will see blind people doing things that surprise and perhaps even confuse you.”

Previous winning projects include teaching blind people to become beekeepers in Uganda, hosting the first conference in Mexico for blind children and their families led by blind professionals, and recording a documentary series called “Planes, Trains & Canes” about navigating and accessing transportation systems in five cities around the world.

For the next step in the contest, Orly is creating an in-depth proposal due by the end of April.

“My talent for cooking, my experiences all over the world tasting a plethora of inspiring favors, and my own story of failure, addiction and abuse woven in with courage, resilience and recovery – it was all for this.”

She Made Canadian Medical History When She Received a ‘Bionic Eye’

Orly Shamir made Canadian medical history when she became the first person in the country to receive a bionic eye.

In a clinical trial six years ago, Dr. Robert Devenyi and his surgical team at a Toronto hospital implanted an Argus Retinal Prosthesis System (Argus II) onto the surface of Orly’s retina.

The Argus II, known as the bionic eye, stimulates the eye with electrodes to transmit visual information captured by a video camera to the patient’s brain. Toronto Western Hospital-University Health Network and Foundation Fighting Blindness provided support as collaborators on the 2014 clinical trial. California-based Second Sight developed the device.

Health Canada approved the system in 2015. It was approved in the United States in 2014 and in Europe in 2011.

Orly has a form of Leber congenital amaurosis called LCA4 caused by a mutation in her AIPL1 gene. She could read large print as a child, but her vision deteriorated to minimal light perception and shadows in her 20s. Now 52, Orly took part in the 2014 trial when she was 46.

Photoreceptors in a healthy retina convert light into electrochemical pulses sent through the optic nerve and into the brain where they are decoded into images. When photoreceptors don’t function properly, as in the case of people with LCA, the first step in the vision process is disrupted and cannot transform light into images.

Approval for an Artificial Retina graphic

The Argus II bypasses damaged photoreceptors through electrodes implanted on the retina. Following the delicate three-hour surgery, Orly wore glasses containing a tiny camera that converted video images into a series of small electrical impulses transmitted wirelessly to the electrodes. Visual information transmits to the brain’s optic nerve when the pulses stimulate the retina’s remaining cells.

The visual improvement does not equal regular sight, but it allows patients to perceive light patterns, observe whether doors and windows are open, or pick up a glass.

Orly worked with rehabilitation experts, low-vision therapists and consultants from Second Sight. Three months following the surgery, she could detect contrast and recognize the difference between white and black. Because patients receive a form of artificial vision through this bionic eye, they need to re-train their brains through rehabilitation to learn and understand messages sent by the device. It’s kind of like learning a new language.

Orly volunteered to take part in the clinical trial for a year but presently does not use the technology.

“I worked hard for two years, then decided to not use the system for personal use, as it didn’t provide any benefits as of yet.”

Orly’s participation is exactly what a clinical trial is all about. She committed to making frequent visits and underwent testing over the course of a year. She knew that the goal of a clinical trial is to see whether a potential treatment is safe and effective, and that, while a trial participant might benefit, the trial’s purpose is to determine if the therapy works.

“I was prepared in being part of advancing technology for blind/visually impaired people in the future. That’s always who I am,” she said. “I’m 100 percent ready and available to get updates and keep trying.”

All About Clinical Trials

Clinical trials are never done in a vacuum, or in a medieval basement where Dr. Frederick Frankenstein (pronounced Fronkensteen), his pretty lab assistant, Inga, and faithful houseboy, Igor, create a monster.

While the creature from the 1974 movie “Young Frankenstein” turns out to be somewhat civilized, (see Gene Wilder as the young doctor and Peter Boyle as the monster doing the soft-shoe in white tie and black tails to “Puttin’ on the Ritz”), a caption above that lab team in a slide shown at the Hope in Focus (formally Sofia Sees Ho p e) second LCA Family Conference cautions: “Regulatory Oversight is Critical!”

Humor credit goes to Ben Shaberman, Senior Director of Scientific Outreach and Community Engagement for Foundation Fighting Blindness. He moderated a four-member panel discussion in a session called “All About Clinical Trials” at the July conference in Philadelphia. Shaberman reports on retinal research for the Foundation’s print and electronic publications. He also presents scientific advancements at local and national events and enjoys working with constituents to help them understand their retinal disease and current research that may benefit them.

Making sure trials are safe

Dr. Wiley Chambers II, MD

Panelist Dr. Wiley A. Chambers, the U.S. Food and Drug Administration’s Supervisory Medical Officer in the Office of New Drugs, said terrible outcomes can happen in trials not approved and regulated by the FDA.

Dr. Chambers previously cited a disastrous case in which a 77-year-old woman traveled to an alleged clinic to have “stem cells” injected in her eyes in the hope of a cure or at least help for her macular degeneration. The procedure entailed separating “stem cells” from the woman’s belly fat and injecting them into her eyes to supposedly regenerate tissue. Not covered by insurance and not federally regulated, the procedure cost almost $9,000 and caused her vision to badly deteriorate after her retinas peeled away from her eyes.

The FDA assigns an Investigational New Drug (IND) number to every legitimate clinical trial.

“Just be careful when you go to a clinical trial or a physician that it is a legitimate trial,” Dr. Chambers said. “If they can’t give you an IND number, then walk away.”

The website Clinicaltrials.gov includes trials that do have an IND number and unregulated trials that do not have an IND number. Avoid them. One must specifically ask if they have been issued an IND number, signaling the federal OK to proceed with clinical studies that happen in three phases.

Dr. Chambers also noted that trials are not for the benefit of participating patients. At the heart of a clinical trial is that researchers do not know what’s going to happen. A key word here is equipoise – a balance or counterbalance – of something.

“We do the clinical trial and find out, does this have some efficacy and is it safe?”

Clinical trials tell as much information as possible, balanced with a doable study and doable patient commitment.

“It’s a balancing act,” he said. “The trials are to help inform people afterward.”

A long, expensive process

Research studies in humans are for potential therapies; they take 10 years or more to complete and can cost tens or hundreds of millions of dollars.

It took 12 years and $500 million to research and develop LUXTURNA™, an engineered virus delivered by subretinal injections of the human RPE65 gene, a gene that, when mutated, causes a form of LCA called LCA2 (RPE65-LCA).

Tami in a pink shirt and Michael besides her in a bright orange shirt sitting at the 2019 LCA Family Conference — Tami and Michael Morehouse

Panel members Tami Morehouse and her husband, Michael, experienced firsthand what it feels like to take part in a Phase 1/2 LCA/RPE65 gene therapy trial. Intervention at earlier ages can offer better results with degenerative diseases like LCA and other inherited retinal diseases (IRDs) because photoreceptors diminish with age.

The Cleveland-area couple talked about Tami’s pioneering experience as the oldest person, at 44, to take part in the LUXTURNA trial and regain some vision.

“It’s a huge, life-changing event for us,” Michael said.

Walking in Philadelphia three days after her first injection, Tami asked her husband if a building up ahead had stripes on it. Turns out, it was a parking garage with spaces between levels appearing as solid stripes. Before the injection, she could not see any part of the parking deck; her ability to discern solids and stripes meant the treatment already began improving her vision.

Tami had some vision in college and walked across the graduation stage by herself. Michael described her progressive vision loss as, “Go on, go on, big drop; go on, go on, big drop; no diagnosis.

“She was on a path to darkness and she knew it,” he said.

Taking the risk for the reward

He heard Jean Bennett, MD, PhD, on a Sunday radio show talking about her retinal research on the emerging therapy that came to fruition as LUXTURNA. He called her office early the next day, and said to the audience, “Guess who answered the phone?” (Here’s a link to a story on Dr. Bennett’s presentation at this conference.)

Seven months later they received an email from Dr. Bennett, with the subject line: “Are you ready?”

Dr. Bennett conducted the studies with her partner in research and in marriage, Dr. Albert M. Maguire.

In answer to a question about what she was thinking before beginning the trial, Tami said, “I don’t want to go totally blind.”

“In all honesty, I never thought that I’d ever have a shot at seeing … I kind of underestimated my possibilities. I became a much more functional person in day-to-day living. I would see who’s approaching. See my kids, my (softball-playing) daughter dancing off third base, taunting her catcher.

“I got way more than I anticipated.”

Tami is part of the Sofia Sees Hope Family Connections program, calming fears and sharing her experiences with many patients along the way, including very young ones.

“Even though huge strides have been made in clinical trials, they’re very frightened, they’re very nervous.

“Jean and Albert explained so much; they relieved my fears in such a way that I’ve been able to transmit that to families, to moms. It’s a lot of pressure for some moms.

“Just being able to say that it won’t hurt when Dr. Maguire inserts a needle in your eye because you’re out like a light; that is a beautiful thing because you don’t even know what’s happening to you.”

Tami advised potential surgical patients and their parents that even though undergoing surgery has the potential to do such good by improving vision, they should think about their expectations. “We are comfortable in our own zone; give us a little bit of change and it can throw us off.”

“If mom and dad or older siblings are calmer, the children are going to be more comfortable, too.”

Setting realistic expectations

Panelist Dr. Michel Michaelides, a founding member and head of clinical ophthalmology at MeiraGTx based in New York City and London, said clinical trials impact the daily lives of study participants because they’re required to undergo multiple tests, many of which, he said, are boring and tedious.

“We spend a lot of time letting people know what they’re really in for.”

Dr. Michel Michaelides, a Founding Member and Head of Clinical Ophthalmology at MeiraGTx

Dr. Michaelides is the Principal Investigator of four interventional clinical trials and has 10 ongoing ethically approved studies. He is Professor of Ophthalmology at London’s UCL Institute of Ophthalmology in the Department of Genetics and Molecular Therapy, and Consultant Ophthalmologist at Moorfields Eye Hospital in the Departments of Inherited Eye Disease, Medical Retina and Pedriatric Ophthalmology.

Moderator Shaberman asked him what he says about therapy options to people who have lost a lot of vision. In advanced cases of vision loss, Dr. Michaelides said, optogenetics might be a relevant course of action. Optogenetics is the science of making cells in the retina that do not normally detect light, become light sensitive, and thereby aim to replace the lost light-sensitive cells (rods and cones/photoreceptors).

“The idea is to make cells that are not light sensitive, (be) light sensitive.”

Another course is retinal implant technology, also known as the “Bionic Eye” or “Artificial Vision,” in which doctors insert a light-sensitive microchip into the retina to provide a way to detect light. These implants can be placed on the surface of the retina (epi-retinal implants) or underneath the retina (sub-retinal implants). He also suggested the use of internal or external cameras with these implants, saying, “I think there’s going to be greater development in that area.”

Another avenue is stem cell therapies (cell therapies), in which donor cells could be used to grow fresh retinal cells for transplantation into the eye to replace lost cells.

He also is involved in the development of therapies using stem cells to replace lost light-detecting retinal cells. He has been Principal Investigator of the first ocular stem cell therapy trial, which involved transplanting retinal pigment epithelial cells (non-light-detecting cells) in patients with advanced St a rgardt Disease.

His clinical trial for a potential LCA4 (AIPL1-LCA) therapy currently is recruiting participants.

Dr. Michaelides’ ocular research comprises 300 peer-reviewed publications and 25 book chapters. One of those research papers came into focus at the LCA conference in July, where an audience member – a mother of a child with LCA2 (RPE65-LCA) – told her story.

“Even after an ERG (electroretinography),*” she said, “nobody told us it was LCA.”

She said reading one of his research publications on RPE65 put her family on the right track.

“That’s what we took to our doctor,” she said. “So, you’ve been really important to our journey.”

The Road to Treatment: Understanding How Therapies Are Developed

Successful clinical drug trials are a cornerstone of U.S. Food and Drug Administration approval, such as with LUXTURNA™, a ground-breaking genetic therapy that helps restore vision in Leber congenital amaurosis (LCA) patients with a mutation in their RPE65 gene (LCA2).

But the FDA’s Dr. Wiley A. Chambers II cautioned LCA families and patients at a recent LCA Family Conference hosted by Hope in Focus (formally Sofia Sees Hope) to make sure their clinical trial of interest is real and not bogus.

Clinical trials drive research with the goal of finding treatments or cures that need FDA approval before commercial use. Twenty-three gene-based clinical trials targeting 13 genes are underway, including an LCA4 (AIPL1) trial, according to Foundation Fighting Blindness. More than 20 retinal cell therapy trials are in progress, and another 100 genes are under investigation in the preclinical pipeline, the Foundation reported.

Dr. Wiley Chambers II, MD

Chambers is supervisory medical officer in the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research. The center’s mission is to assure that safe and effective drugs are available to the American people.

He was among three panelists who joined moderator Jeffrey Finman, PhD., of Jupiter Point Pharma Consulting, in exploring the development and approval of new treatments for rare diseases, including LCA. The panel was part of Sofia Sees Hope’s first-ever LCA Family Conference in Groton, CT, on Oct. 6.

Jennifer Hunt with Editas Medicine, a discovery-phase biotechnology company, and Tami Morehouse, a participant in the breakthrough LCA2 (RPE65) genetic therapy trial joined Chambers on the panel.

Not all trials are ‘real’

“Be aware of any trial where you’re charged for the drug or biologic product,” Chambers said. “If they’re charging you, watch out.”

He said every clinical trial is assigned an Investigational New Drug (IND) number. No number, no real trial.

Chambers sited the disastrous case of a 77-year-old woman who traveled to Georgia to have stem cells injected in her eyes in the hopes of a cure or at least help for her macular degeneration. The procedure entailed taking fat from the woman’s belly, separating stem cells that naturally occur in fat, and injecting them into her eyes to regenerate damaged tissue.

The procedure, not covered by insurance and not approved by the FDA, cost the woman $8,900. Within three months, her retinas – the eye’s layer of light-sensitive cells – had peeled away from the rest of her eyes. Her vision deteriorated to where she only could see hand movement before her eyes. She no longer could find her way on her own.

Risks vs. benefits

To fulfill its mission, the FDA monitors the drug development process during investigational stages, approves new drug products that are safe and efficacious, and monitors post-approval adverse events.

The FDA does not conduct clinical studies, choose which products a company will study, force companies to market products, or regulate the practice of medicine.

Approval depends on whether the benefits of a drug outweigh the risks.

“There is always a risk,” Chambers said. “If it does anything positive, it does something negative…It’s a balancing act.”

The factors weighed in this balancing act of forces and interests, clinically referred to as equipoise, consist of:

the potential benefit from the drug product;
the potential adverse event from drug;
the potential safety from not taking a new drug;
the potential loss from disease condition if not taking an effect therapy;
and missing out on an alternative therapy.

Exploring different routes to a cure

Panelist Jennifer Hunt, vice president of clinical operations for Editas Medicine, described the process of developing a medicine that corrects mutated genes through editing. Using her company’s investigational medicine, EDIT-101, as an example, she detailed the course for finding an ocular medicine to treat patients with LCA10 (CEP290). LCA10 is one of the leading causes of blindness beginning in the first years of life.

Editas is working on developing CRISPR-based medicines (pronounced crisper, and meaning Clustered Regularly Interspaced Short Palindromic Repeats). CRISPRs are specialized stretches of DNA; the protein Cas9, meaning CRISPR-associated, is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA, according to LiveScience.

EDIT-101 is poised to be the first in vivo CRISPR medicine used in human trials. Before those clinical trials begin, researchers have been looking to answer key questions, such as, does editing restore protein expression in cells and what are the best clinical trials for patients?

Editas researchers also are conducting an ongoing natural history study with 40 patients, ages 3 and older. They are followed up with six times over the course of a year at seven sites – four in the United States and three in Europe – to characterize them, assess their vision changes and validate study endpoints.

Editas has stated it plans to file an Investigational New Drug (IND) application with the FDA in October. Once allowed by the FDA, Editas can begin clinical trials.

The FDA evaluates three study phases of a proposed new drug:

Phase 1 investigation of new drugs in humans is a phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to determine the drug’s most frequent and serious adverse events and, often, how the drug is broken down and excreted by the body. These trials usually involve a small number of participants.
Phase 2 consists of research to describe clinical trials that gather preliminary data on whether the drug is effective in people who have a certain condition/disease. Participants receiving the drug may be compared to similar participants receiving a different treatment, usually an inactive substance, called a placebo, or a different drug. Safety continues to be evaluated, and short-term adverse events are studied.
Phase 3 research is to describe trials that gather more information about a drug’s safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. These studies typically involve more participants.

The human side of a drug trial

The third panelist, Tami Morehouse, spoke to the safety and effectiveness of LUXTURNA, a medication developed by Spark Therapeutics that the FDA approved last December for commercial use. Tami made medical history at age 44 when she became the oldest person to participate in the successful Phase 1 LCA-RPE65 genetic therapy clinical trial in 2009.

Dr. Jean Bennett and her husband, Dr. Albert Maguire successfully used the treatment on Lancelot, a dog born blind with a mutation in his RPE65 gene, before testing the medication on humans.

Prior to the trial, Tami could see faces, but much of the time she saw dark, gray haze. She woke up every morning when her alarm clock went off, wondering, would this be the day she would wake up with no vision.

“I had no hope whatsoever,” she said.

Her husband, Michael, added, “That’s where she’d be today were it not for that trial.”

Michael learned of Dr. Bennett and her ongoing clinical trials at Children’s Hospital of Philadelphia (CHOP) from a radio broadcast.

The trials resulted in FDA approval of LUXTURNA, a gene therapy that enabled Tami to regain some of her vision.

“It was an incredible experience that was a long time coming,” she said.

Tami said she is “walking, living proof” of the treatment’s safety and effectiveness. She told her audience to keep in mind that older people, along with children and young adults, can benefit from the treatment.

“Don’t give up hope and keep looking.”

IRD Milestones: Reasons to Be Excited

1971 – Just those numbers in white on a black page appeared on the big screen.

That’s how Brian Mansfield, PhD., began his presentation to families and patients living with Leber congenital amaurosis at Hope in Focus (formally Sofia Sees Hope) LCA Family Conference on Saturday, Oct. 6, in Groton, CT.

The year on that otherwise empty page marked the founding of Foundation Fighting Blindness – a time when patients losing vision often heard, “Go home. Learn Braille. You are going to go blind.”

Mansfield’s audience at the conference was made up of people diagnosed with a variety of rare inherited retinal diseases, including LCA, their caregivers and relatives, and representatives of various bio-tech and pharmaceutical companies working in the IRD arena. It was Sofia Sees Hope’s first such conference.

Dr. Brian Mansfield

Mansfield is the foundation’s senior vice president of research. He brought his audience up to date with information about clinical trials for inherited retinal diseases (IRDs), the rich preclinical therapeutic pipeline, how the Foundation uses money to move treatments forward and what people can do to drive change for IRD treatments and therapies.

His presentation culminated in a projected slide filled with logos of bio-technology and pharmaceutical firms, many of which are in contact with the Foundation, and represent the ever-expanding research and development field to help people with visual impairment.

$725 million in funding

In its 47 years, Foundation Fighting Blindness has raised more than $725 million toward research, development and public health education. It partners with several dozen U.S. non-profit organizations, including Sofia Sees Hope.

Mansfield traced the rapid trajectory of identifying genes causing retinal disease, from the founding of the National Eye Institute in 1968 through the Foundation’s funding of the Berman-Gund Laboratory for the Study of Retina Degenerations in 1971. It included the 1989-90 work identifying the rhodopsin gene as the genetic cause of Retina Pigmentosa (RP), and conducting the first retinal disease gene therapy trials in 2007. And of course culminated in last December’s federal approval LUXTURNA™, a gene therapy that helps restore vision in people with LCA2 (RPE65).

For people affected by LCA, more than 80 percent can now get a clear genetic diagnosis. For IRDs, more than 260 retinal disease genes have been identified, and the overall success in providing a clear genetic diagnosis is 65 percent.

Mansfield said that 23 gene-based clinical trials targeting 13 different genes are currently underway, including the LCA4 (AIPL1) gene trial by MeiraGTx.

A promising pipeline

He said the gene therapy preclinical pipeline is promising, with 100 genes under investigation. Researchers also are conducting preclinical studies of optogenetic gene therapies, in which light is used to control genetically modified retinal cells.

ProQR is planning a pivotal Phase 2/3 gene patch clinical trial for the LCA10 (CEP290) gene that involves injecting a short DNA molecule to cover up the faulty instruction the gene otherwise gives to act incorrectly. Also, Mansfield said, Editas Medicine is close to gene editing clinical trials, called “cut and paste” because an enzyme seeks out and repairs the defective gene. Another editing therapy in the pipeline, called base editing, essentially backspaces over the mutation and types the correction over it.

Also underway are more than 20 retinal cell therapy trials in which lost cells are put back to replace missing cells or used as biofactories to produce factors that help stabilize the retinal cells.

To help propel research and trials, the Foundation funds Career Development Awards to attract and retain clinician researchers dedicated to retinal disease research. The Foundation also provides awards to the brightest minds in the field, individually or as a team, to drive research.

It also gave 16 years of preclinical research support amounting to $10 million toward Spark Therapeutics’ commercial gene therapy, LUXTURNA, the first directly administered gene therapy approved in the United States that targets a disease caused by mutations in a specific gene – LCA RPE65.

Mansfield talked about how Applied Genetics Technology Corp. (AGTC) leveraged an early Foundation investment to garner $265 million to develop genetic therapies, some of which are in clinical trials.

The Foundation also supports 20 centers – the International Clinical Consortium – that have standardized assessment protocols for clinical trials.

Patient involvement is key

To continue to attract industry interest, Mansfield detailed the Foundation’s My Retina Tracker registry, with its tagline “Track your vision. Drive the research.” It’s a free, secure, online patient registry that notifies registrants of clinical trials and gives researchers access to their disease data – but not their personal information – to advance studies on any number of research and therapy development efforts associated with IRDs.

The power of My Retina Tracker is optimized by registrants getting a genetic diagnosis. Sofia Sees Hope donated $65,000 to help people receive genetic testing and counseling.

Mansfield emphasized to his audience the vital importance of their knowledge, what they carry with them, and that patient input is critical to drug development.

Curing Blindness: The Road To Treatment With LUXTURNA™

This is the first in a series following the progress of Creed Pettit, a 9-year-old Florida third-grader, who is a candidate for the breakthrough gene-therapy drug called LUXTURNA™, approved as the first gene therapy for Leber congenital amaurosis (LCA), and as the first-ever genetic therapy in the United States for an inherited disease.

A birthday wish for 9-year-old Creed Pettit, diagnosed with LCA-RPE65, comes closer than ever to coming true today when the Florida boy and his mom meet with a surgeon to schedule treatment with LUXTURNA™, the just-approved, revolutionary gene therapy that corrects his specific gene mutation.

Creed smiling and holding up a piece of paper that writes, "My last birthday with LCA! #RPE65 #CREED — Creed, LCA2 *RPE65*

Creed had wished that his January 9th birthday would mark his very last with LCA-RPE65.

This third time might truly be the charm for Creed, as his mom, 41-year-old Sarah St. Pierre-Pettit of Mount Dora, Fla., twice tried to get her son, at ages 3 and 4, into clinical gene-therapy trials in Iowa. He was not approved for the trial because he could not perform steps required by the study, such as trying to navigate a maze.

Sarah learned a few days ago that her insurance company gave the go-ahead to schedule the surgery that costs $850,000.

“No more hurdles,” she wrote in an email. “I am a wreck of happy tears!!!”

Sarah and her son drove to Miami’s Bascom Palmer Eye Institute to meet today with Dr. Audina Berrocal to discuss the procedure and answer questions.

Brand new treatment

It was last October when decades of research culminated in a Food and Drug Administration advisory committee hearing in which the group recommended approval of LUXTURNA™, Spark Therapeutics’ breakthrough gene-therapy treatment.

“One of the doctors spoke about my son in the FDA approval process, which was just amazing,” Sarah said. “That day I knew Creed could be treated.”

Creed and his mom Sarah sitting on steps. — Creed and his mom, Sarah St. Pierre-Pettit of Mount Dora, Fla. Creed meets with his surgeon Feb. 19 to schedule his treatment with LUXTURNA to reverse his blindness caused by LCA-RPE65.

Hope in Focus (formally Sofia Sees Hope) founder and board chair Laura Manfre also counted among those speaking on behalf of this ground-breaking treatment, sharing with the committee a story of a woman whose vision greatly improved in the clinical trials and changed her life.

The FDA granted approval of the treatment in December, paving the way for patients like Creed with LCA-RPE65 to receive, LUXTURNA™, the first genetic therapy treatment for an inherited retinal disease (IRD), and the first genetic therapy in the United States created for any inherited disease.

RPE65 is a form of Leber congenital amaurosis in which the body can’t make a protein needed by the retina to convert light into vision-enabling signals, which are sent to the brain. This new therapy involves injecting under the retina a human-engineered virus containing copies of a normal gene, so cells can express the protein. LCA is a rare inherited retinal disease, and nearly 30 gene mutations are associated with it.

Creed said that after the surgery, he can’t wait to see a real rainbow and he can’t wait to throw his canes in the lake.

His mom, on speakerphone last week while driving to pick up a new batch of “Creed’s Cause” T-shirts that she designed, talked about her most recent effort to help pay for medical bills not covered by insurance, and for travel expenses.

At $20 apiece, Sarah sells them locally and through Facebook and Instagram. When she’s not making T-shirts, she’s an elementary school physical education assistant, and hosts trivia nights at a brewery owned by her sister and brother-in-law.

Creed is a third-grader at Mount Dora Christian Academy, a school that better serves his needs than the public system. MDCA is like family to Creed and his mom, hosting lots of fundraisers, including a January basketball event that raised $5,000. The Douglas G. Halliday Foundation of Orlando recently made a generous contribution, adding to the more than $100,000 raised from 5K races, a CrossFit event and contributions from many friends and people she doesn’t even know.

Missing milestones

In 2011, doctors diagnosed Creed with LCA; in the months following he received a genetic diagnosis of LCA-RPE65. Image: Toddler-aged Creed wearing patches over both eyes.

Sarah knew something was wrong with her baby shortly after he was born in January 2009.

“He missed all of the milestones. He would run into everything. He wasn’t walking. Instead, he did this weird Army crawl. He’d feel for his food and look up.

“Everything just said something’s not right.”

Then came the heartache of trying to figure out what was wrong. Doctors diagnosed Creed at 18 months old as autistic, and another said he had problems with his peripheral vision.

For the first year of Creed’s life, his mom thought he had colic because he would spend his days contentedly on a blanket outside, and at the end of the day when he went back into the house, he cried, all night.

An autism teacher advised Sarah to black out all the windows in the house, keep everything dark and not allow him to be in light, the exact opposite of what he needed.

She found the right advice from a woman specializing in depth perception and dyslexia. For the first time, and coming from a non-doctor, Sarah learned that her son probably was blind.

Creed with eye patches on his eyes, his mom is holding him — In 2011, doctors diagnosed Creed at 2 years and 8 months with LCA; in the months following he received a genetic diagnosis of LCA-RPE65. A week later, Sarah began her fundraising endeavors.

She also reached out for support that resulted in a team of therapists and specialists to address Creed’s movement, vision, speech, orientation, mobility and behavior.

Trying for a gene therapy trial

Sarah learned about RPE65 gene-therapy trials. She, her mother, Mary, and Creed traveled to Iowa twice for what turned out to be unsuccessful attempts to be part of the research.

Creed’s visual acuity is actually very good; when he has light, he can see. When he doesn’t have light, he can’t see anything. As Sarah says, “No light, no sight.”

He needed light and he got it, with his mom installing special bright lights all over the house.

“I’m positive they can see us in space,” she said of the lights in and around her home. Creed also has more light in school, including a light in his desk.

At school and in life, Creed has another light shining on him – his best buddy Michael, who bonded with him in first grade. He helps him be safe and gives Sarah updates about her son.

She said she can’t believe Michael’s maturity and sensitivity and believes he was put on this earth to help her son and others.

For Valentine’s Day, teachers filled bags with candy and sold them for $1 each, with proceeds going toward Creed’s expenses.

The words on the candy bag say, “Help Creed see how much we love him.”