Author: Eve Orcutt

Connecticut Rare Disease Day 2020

Rare Disease Day banner with zebra stripes. "Make an Impact on Rare Disease Day! Show Your Stripes."

The end of February signals the time to focus awareness on rare conditions by celebrating Rare Disease Day, a global event addressing the thousands of rare diseases that affect one in every 10 Americans.

Rare medical conditions affect 300,000 people in Connecticut, the home state of Sofia Sees Hope, and 30 million nationwide.

Yes, those are astounding figures that call for astounding action to bring attention to the needs of people living with rare diseases, such as Leber congenital amaurosis (LCA), one of the more than 7,000 rare diseases. The day – and its events that happen nationally and in more than 85 countries – fosters awareness needed to drive research for cures and treatments for rare diseases often overlooked by health-policy decision makers and the medical community.

In Connecticut, people living with rare disorders and their families, along with lawmakers, caregivers, advocates, advocacy organizations, healthcare providers, industry leaders and researchers will gather at the Capitol in Hartford to celebrate Rare Disease Day 2020 by highlighting their concerns and seeking help for solutions from state lawmakers.

Sofia Sees Hope plans to relay rare disease advocacy information, including the importance of genetic testing, to legislators on behalf of people living with LCA and other rare inherited retinal diseases (IRDs).

The public is invited to attend this legislative forum and breakfast at the Legislative Office Building, 100 Capitol Ave., Hartford, from 8 a.m. to 11 a.m., Friday, Feb. 28, the last business day before 2020’s official Rare Disease Day, Saturday, Feb. 29. The event takes place in the building’s second-floor atrium that looks out to the gold-domed Capitol building.

The National Organization for Rare Disorders (NORD) is the U.S. sponsor for Rare Disease Day 2020. The Hartford gathering, as with many others across the nation, is organized by NORD and its Rare Action Network (RAN). The focus for this year’s Rare Disease Day is the impact that rare diseases have on patients, families, caregivers, healthcare providers and local communities.   

For more information about this free event, please contact Lesley Bennett, RAN’s Connecticut Volunteer State Ambassador at Lesley.bennett@rareaction.org or 203-829-7650. Also, here is a link to information on all states regarding RAN and Rare Disease Day: https://rareaction.org/resources-for-advocates/state-profiles/

Here’s a look at the prospective speakers 

Dominic Cotton, a father and advocate for those with rare diseases and brain injuries, will emcee the event that begins after the 8 a.m. sign-in and breakfast.

Heidi Ross, NORD’s Director of State Policy, will offer opening remarks, followed by the legislative welcome by state Rep. Jonathan Steinberg, Co-Chair of the General Assembly’s* Public Health Committee; Rep. Michelle Cook,* member of the Public Health Committee; Sen. Len Fasano, Senate Majority Leader; and Jean Kelly of Brian’s Hope, a non-profit she and her husband, Jack, founded in 2012 for their son, Brian, diagnosed at age 6 with Adrenoleukodystrophy (ALD), an x-linked metabolic disorder. The couple advocated for mandatory ALD newborn screening in Connecticut, which was passed as law in June 2013. 

Dr. Karen Rubin, a pediatric endocrinologist at Connecticut Children’s Medical Center (CCMC), and Adrienne Manning, Connecticut’s Newborn Screening (CT NBS) Program Division Director in the Department of Public Health Laboratory, will address diagnoses and treatments in newborns. State law requires all newborns to be screened for certain genetic and metabolic disorders. The program’s efforts help prevent disability and premature death by ensuring newborns receive the screening and, when needed, evaluation and treatment.

Dr. Rubin and Manning are part of a new partnership between the NBS Program and CCMC called the Connecticut Newborn Diagnosis and Treatment Network.

Silvia Vilarinho, MD, PhD, and Donna Sciacca of the American Liver Foundation are  scheduled to talk about rare liver disorders. Dr. Vilarinho, Assistant Professor of Medicine (Digestive Diseases) and of Pathology at Yale University, is a physician-scientist who uses genetics, genomics and human samples to investigate the molecular basis of various liver diseases of unknown causes. Sciacca is the Community Outreach and Education Manager for the foundation’s Connecticut division.

Dr. Joanna Gell of Jackson Laboratories and CCMC will address germ cell tumors, which can be cancerous or noncancerous growths that form from reproductive cells. Dr. Gell is Assistant Professor in the Department of Pediatrics at the UConn School of Medicine.

Dr. Charles Whitaker, a neurologist who sees patients at the Hospital for Special Care (HSC), will talk about adult neuromuscular disorders.

Laura Morris, mother of a patient with epidermolysis bullosa (EB), a group of rare genetic conditions that result in easy blistering of the skin and mucous membranes, will appear with Rep. Russ Morin, who authored legislation that helped EB patients. Morris is Outreach Coordinator for the state’s Office of Health Strategy.

Dan Donovan, Co-Founder and CEO of rareLife solutions, will address the scarcity of literature on rare diseases.

Father Nikolas Karloutsos will moderate a pediatric panel about the impact of pediatric rare diseases on families. He is a caregiver for his daughter who has a BRAF mutation Rasopathy – probably Cardiofaciocutaneous (CFC) Syndrome – which causes issues with behavioral health and cognition. 

Taking part in the panel will be: 

  • Heather Knapp, caregiver and mother of four, whose youngest was identified at birth through the NBS Program with Phenylketonuria (PKU), an inherited disorder that increases the levels of a substance called phenylalanine in the blood. If untreated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems.
  • Jim Kubicza, who has a son with Angelman syndrome, a complex genetic disorder that primarily affects the nervous system.
  • Information that will be shared on behalf of Marissa B., mother of a child with CDKL5, a neurodevelopmental and epileptic encephalopathy disease characterized by difficult-to-control seizures that begin in infancy, followed by significant delays in many aspects of development. She and her husband provide 24/7 care for their child, who is among those on a years’ long waiting list for a special children’s waiver for Medicaid coverage.  

A panel on the impact on adults with rare diseases will follow, and includes:

  • Carmen Wooster, mother of a daughter with Stiff Person Syndrome (SPS), a rare, progressive syndrome that affects the nervous system, specifically the brain and spinal cord.
  • Beverly St. Onge on Common Variable Immune Deficiency (CVID), one of the most frequently diagnosed primary immunodeficiencies, especially in adults, characterized by low levels of serum immunoglobulins and antibodies, which cause an increased susceptibility to infection.
  • Input on DiGeorge syndrome, a chromosomal disorder that results in poor development of several body systems.
  • The Leeds family regarding hereditary angioedema, a disorder characterized by recurrent episodes of severe swelling.

Paul Pescatello is also set to speak. Pescatello is President and CEO of the New England Biotech Association and chairs Connecticut Business & Industry’s Bioscience Growth Council.

Living with Leber Congenital Amaurosis: Dami’s Story

I was born in 1976 in Spokane, Washington. By the time I was born, my parents’ relationship was basically over, so I was raised by a single mom. It was clear from a very young age that I had significant vision loss. I started wearing glasses at 18 months. I went through lots of grueling tests as a toddler to figure out the cause of my vision loss with no real answers. Despite this, I lived a very full life. I was a Girl Scout. I did gymnastics. Basically, I did everything my friends did.

When I was 10, my mother took me to a research hospital in Portland, Oregon. After two days of testing, they told my mother I had Leber congenital amaurosis type 1. They told her I would likely be totally blind by the time I was 17.

So, I lived my days after that doing and seeing what I could because my vision had an expiration date. I didn’t just do the same stuff as my friends. I did more. I also got involved in the blindness community. I did public speaking in high school. I worked with blind kids, noticing that parents were not doing their children any favors by treating their children like fragile flowers. I worked with children with so few social skills because their parents didn’t expect them to act like the other kids. All that did was hurt them. But, I digress from my story.

So, I turned 17, and I could still see. Now, instead of vision having an expiration date, every day with vision was a gift. I went to college and met an amazing boy. We were married and pregnant with our first child within a year of meeting because I couldn’t stand the thought of not seeing my baby’s face.

I could go on forever about my life, but most of it is only interesting to me, so I’ll fast forward. I am 43, still married to that amazing boy, and we have two amazing boys of our own. I earned a Master’s degree in communications, and I work for a state agency that does vocational rehabilitation for people with visual impairments. I also still have a decent amount of vision, from my perspective.

A few weeks ago, I read a Facebook post about genetic testing. Nobody had ever talked to me about this before. I have regular eye appointments, but they really just check my vision and cataracts. I want to know more. I have started thinking I may have been misdiagnosed years ago, but I don’t even know where to begin. I’ve signed up for the genetic databases, but now what? It is such a strange feeling to doubt the one thing that had seemed certain my whole life.

So, that’s me. I’m not inspiring or pitiful. I’m just me, trying to figure out where I go from here and so glad to know I’m not alone.

Giving Tuesday: Help Provide Access to Free Genetic Testing

When our daughter Sofia was 2, we knew something was wrong with her vision. By the time she was 5, doctors told us she perhaps had Leber congenital amaurosis (LCA), and the prognosis was grim: total blindness by adulthood. They did say that if we could confirm her condition genetically, there might be a chance for treatment. So for more than seven years, we underwent genetic testing in the hopes of determining which genetic variation was causing her vision loss.

That was more than five years ago. Since then, so much has happened, ranging from our decision in 2013 to create Hope in Focus (formally Sofia Sees Hope) to fund research into treatments, to the fact that in 2019, a child can be diagnosed with a specific type of LCA and receive treatment to restore vision within the same year.

In the time since we learned of Sofia’s diagnosis, 27 different genetic variations have been identified as causing LCA. One – RPE65 – has an FDA-approved treatment that has been performed on dozens of patients with great results. More good news: there are more than 30 clinical trials currently underway for inherited retinal disease, including several promising LCA treatments. But our work is not done. There are 26 LCA genetic variations still awaiting an approved and effective treatment. In the last week alone, we’ve heard from two individuals who have been turned down by insurance for genetic testing to
diagnose their retinal disease.

On this Giving Tuesday (December 3), we are asking for your help in making sure that every single person whose doctor tells them they have an inherited retinal disease has the ability to access a genetic test, easily and at no cost. To date, we have donated $105,000 to make it possible for families to access free genetic testing. That’s more than 100 patients we’ve helped open the door to the next steps in their journey. But there are many more still facing a closed door. We want to open it.

Between now and December 31, every dollar you donate to Sofia Sees Hope will go toward supporting free genetic testing. We thank you in advance for your support.

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 Hope) 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 headshot
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.”

Black and White headshot of Dr. Michel Michaelides
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 Stargardt 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.”

Retinal Disease Gene Therapy Breakthroughs Trace Their Roots to 19th Century Research

Theodor Karl Gustav von Leber would be proud. So would Adolphe Franceschetti and Carl-Henry Alström. 

Their research from the 19th and 20th centuries laid the foundation for groundbreaking gene therapy to treat Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs). Translational research focused on LCA helped bring forth unprecedented numbers of genetic clinical trials now underway for IRD treatments and cures.

Dr. Tomas S. Aleman, associate professor of ophthalmology and director of the Hereditary Retinal Degeneration Clinics at the Perelman Center for Advanced Medicine and the Center for Advanced Retinal and Ocular Therapeutics at the University of Pennsylvania, discussed the beginnings of research into retinal degeneration as part of his presentation at the Hope in Focus (formally Sofia Sees Hope) second LCA Family Conference in Philadelphia last summer.

Dr. Aleman joined three panelists in a conference session called “One Disease, Many Approaches,” moderated by Brian Mansfield, PhD, executive vice president of research and interim chief scientific officer for the Foundation Fighting Blindness. 

In a research paper published in 1871, Dr. Theodor Karl Gustav von Leber recognized early-infancy severe retinal disease with pupils that are “amaurotic,” related to amaurosis, meaning dimming, darkening, dark or obscure. Amaurotic pupils do not relate to light normally, expanding and contracting more slowly than normal or not responding to light at all. A large group of early-onset inherited retinopathies causing blindness carry his name as Leber’s Congenital Amaurosis. 

“His descriptions still endure,” Dr. Aleman told his audience of more than 80 people from across the country and Mexico.

The evolution of research

Dr. Tomas S. Aleman, associate professor of ophthalmology and director of the Hereditary Retinal Degeneration Clinics at the Perelman Center for Advanced Medicine and the Center for Advanced Retinal and Ocular Therapeutics at the University of Pennsylvania

Dr. Adolphe Franceschetti authored more than 500 articles throughout his life (1896-1968), realizing the retinal origin of the blindness and working on ocular genetics, Dr. Aleman said. A specific behavior comprised of poking, pressing and rubbing the eyes with a knuckle or finger to mechanically evoke perception of light is called Franceschetti’s oculo-digital sign and is characteristic of LCA. Researchers suspect this behavior in affected children may contribute to deep-set eyes and keratoconus, a condition in which the normally round cornea thins and bulges into a cone-like shape, causing distorted vision.

Dr. Carl-Henry Alström confirmed that LCA is genetic in nature, and he is credited with recognizing in the 1950s syndromic forms of LCA and other early-onset retinopathies such as Bardet-Biedl Syndrome, a rare genetic disorder with highly variable symptoms that may include retinal degeneration, obesity, reduced kidney function and many other features.

LCA occurs in 1 in 30,000 to 1 in 80,000 people and makes up 5 percent of all retinal dystrophies. Twenty percent of children with visual impairment and attending special schools have LCA.  

LCA, thought of as one disease until 40 years ago, now consists of more than 27 forms.

“It’s a large pack of diseases,” Dr. Aleman said.

Decades of work toward success

He characterized LCA as a molecularly heterogenous or diverse group of diseases with most primary disease location within the cells that perceive light or photoreceptors. Dr. Aleman detailed the complexities of clinical exams, vision testing and the spectrum of severity of vision loss observed in LCA. One such scenario, known as structural-functional dissociation, occurs when the loss of vision is disproportional to the loss of photoreceptors and is frequently seen in LCA, particularly very early in life. Such scenario represents the ideal for gene corrective treatment strategies. 

RPE65-LCA studies led by a group of researchers at the University of Pennsylvania dating back to the late 1990s solidly demonstrated LCA could be treated. Dr. Aleman  cited the importance of the translational research and clinical trials that led to federal approval of LUXTURNA™, a gene therapy treatment for LCA2 or RPE65-LCA, saying other, more frequent and neglected diseases have gotten attention through the RPE65 story.

He singled out two researchers, Jean Bennett, MD, PhD, who joined him on the conference panel, and her partner in research and marriage, Dr. Albert M. Maguire. He pointed out that their foresight and drive pushed research beyond the initial gratification granted by the spectacular results of early multi-institutional RPE65 gene therapy trials, to fulfill the practical need of an approved treatment for use in the clinic. The treatment, which produces dramatic gains in visual sensitivity, is the first and is, to date, the only gene therapy product approved for clinical use for an inherited retinal disease in the United States and Europe.

More patients have been treated with LUXTURNA since its approval in December 2017 by the U.S. Food and Drug Administration than those who received the medication during the clinical trials.

“I like to think that if it wasn’t for Jean and Albert, we wouldn’t be where we are today,” he told the gathering of patients, patient advocates, family members, researchers, doctors and biotechnology leaders.

No cure yet; work continues

Having one retinal gene therapy approved for use in the clinic, 900 patients enrolled in trials across 30 sites, and progress on therapies for the most severe forms of LCA, Dr. Aleman said, “That should stimulate ourselves to continue.”

He noted that much work remains to be done: LCA has not been cured, and researchers do not have a solution for every type of LCA. Gene therapy may not be enough for every patient or form of LCA, and the potential outcomes after treatments should not be expected to be the same across the heterogeneous group of diseases under the LCA umbrella.

In closing his presentation, Dr. Aleman posed three questions regarding LCA treatment and research: 

  • Can we treat hereditary retinal degenerations/LCA? “Yes, the answer is yes.
  • Can we defeat LCA? “And the answer is also yes.” 
  • Do we have the tools and people to do it? “The answer is also yes.”

Dogs as test cases

In her presentation, Dr. Jean Bennett described how the RPE65 gene, when mutated, causes LCA2 or RPE65-LCA. In early research, Briard herding dogs that carried the mutated gene gained improved vision after receiving subretinal injections of an engineered virus of the human RPE65 gene. The treatment works by encoding an enzyme that converts light into electrical signals interpreted by the brain.

Dr. Bennett was one of the first investigators to use viral vectors, in which a virus is used as a vector or carrier that is genetically engineered to deliver the gene to specific cells in the retina. She is professor of ophthalmology at the Center for Advanced Retinal and Ocular Therapeutics and the F.M. Kirby Center for Molecular Ophthalmology at the Perelman School of Medicine. Please see a related story detailing her conference presentation. 

Pam Stetkiewicz, PhD, vice president of program management at Editas Medicine, described a different approach using gene editing technology developed by Editas. The treatment uses molecular biology to create genomic medicine that precisely edits – by locating and removing – the targeted mutation in LCA10 or CEP290-LCA. She said the technology builds on the foundation inspired by Dr. Bennett’s gene replacement therapy.

More treatments in the works
Pam Stetkiewicz, PhD, vice president of program management at Editas Medicine

Editas Medicine, based in Cambridge, Mass., in partnership with Allergan, based in Dublin, Ireland, use CRISPR/Cas9 gene-editing technology to accomplish DNA editing. The treatment, called EDIT-101, cuts out the mutation and is delivered to photoreceptors by subretinal injection. The editing permanently corrects the original, non-functioning protein essential for vision.

Dr. Stetkiewicz said Editas hopes to use the medicine to treat LCA10. Additionally, the company is developing experimental medicines to treat Usher Syndrome 2A and Retinitis Pigmentosa, among other IRDs. Editas is also working to develop engineered cell medicines to treat cancers and blood diseases, including Sickle Cell Disease. 

The FDA approved the company’s 10,000-page data package, securing the required Investigational New Drug (IND) application to begin clinical studies with EDIT-101 in humans.

Editas and Allergan currently are recruiting patients with CEP290-LCA for a natural history study that will create the basis to test safety and efficacy in the Phase 1/2 clinical trial of EDIT-101.

Dr. Stetkiewicz said preclinical data shows that EDIT-101 is well-tolerated, efficacious and safe. Measurement of editing intended DNA versus unintended DNA is called specificity. Human retinal explants, pieces of tissue cultured for growth, treated with EDIT-101 resulted in a high level of intended editing with zero unintended editing, meaning the treatment has an excellent genomic specificity profile.

“So, we’re thrilled with this result,” she said. 

Phase 1/2 clinical trials will begin in the second half of this year with 18 patients age 3 years and older at clinical sites in Massachusetts, Florida, Oregon and Michigan.

DNA, RNA, & LCA
Michael Schwartz, M.S., MBA, is vice president of ophthalmology at ProQR Therapeutics and is the global project leader for Sepofarsen (QR-110), an RNA therapy under development.

Panelist Michael Schwartz, M.S., MBA, is vice president of ophthalmology at ProQR Therapeutics and is the global project leader for Sepofarsen (QR-110), an RNA therapy under development. 

ProQR, based in The Netherlands with offices in Cambridge, Mass., is developing an antisense oligonucleotide (AON) product, Sepofarsen (QR-110), designed as a disease-modifying therapy for LCA due to the c.2991 +1655A>G mutation (p.Cys998X) in the CEP290 gene. The company is developing AON products, which are RNA therapies primarily for ophthalmic inherited disease. AON are short, single-stranded RNA molecules that interact with messenger RNA to prevent translation of a targeted gene.

Sepofarsen works like genetic tape to block the mutation p.Cys998X in the CEP290 gene.

To help understand what this means, Schwartz presented background on DNA, RNA and LCA:

The body comprises many different cells, and we have DNA in each of these cells. DNA contains many instructions for making all the different proteins, which are important building blocks needed by a cell.

When the cell needs a building block, it first copies instructions to a shorter blueprint called RNA; the RNA is then used to guide how to make a new protein, like CEP290. Together, these different proteins make sure the cell works as it should, resulting in normal vision.

But things don’t always go right. Inherited diseases are caused by mistakes in the DNA, and then these mistakes are copied into the RNA, as in the p.Cys998X mutation in CEP290.

This means that the proteins also will have the mistakes in them. They can’t work properly, and the cell cannot function as it should. This is what causes LCA.

He also detailed the workings of RNA therapies, saying they consist of short RNA molecules, with the aim to repair the mutation in a patient’s RNA – without changing the DNA – and to restore the function of the protein and the cell to hopefully improve vision.

A normal CEP290 protein maintains cilium structure in the photoreceptors of the retina and enables normal protein transport to the photoreceptor outer segment.

The CEP290 p.Cys998X mutation creates an environment that results in an aberrant exon that disrupts the splicing code of genes by truncating the CEP290 protein, ultimately leading to the degeneration of the photoreceptor cells.

Sepofarsen, delivered by intravitreal injection, blocks the recognition of the aberrance, and that results in favoring production of normal protein. 

“We can actually reverse the phenotype of that mutation,” Schwartz said.

ProQR is finalizing interim results of its ongoing Phase 1/2 trial involving 11 people from ages 8 to 44. Schwartz said most of the patients had clinically meaningful improvement. The company’s Phase 2/3 trial began, with the first patient dosed in April. The 24-month trial expects to enroll 30 patients.

He cited an exceptional patient responder in the Phase 1/2 trial in which an adult with only light perception vision before the trial could now read letters on the eye chart.

“They said they could see things out of the treated eye that they had not seen for decades.”

Rare Disease Advocacy: There’s Power In Numbers

Tell your story. Tell your story again. Then tell it again.  

That’s the beginning of advocacy for rare disease. 

“You have to be assertive and speak up. You don’t have time to waste!” advocate Terri Booker implored her audience at the Sofia Sees Hope second LCA Family Conference.  

Booker, a lawyer and an advocate for people living with Sickle Cell Disease (SCD), spoke as part of a four-member, patient-advocacy panel called “Your Voice Matters!” moderated by Hope in Focus (formally Sofia Sees Hope) Executive Director Annette Tonti.

More than 80 people from 15 states and Mexico attended the July 27 conference in Philadelphia. The event brought together people living with Leber congenital amaurosis (LCA), inherited retinal diseases (IRDs), SCD, which is a group of inherited blood disorders, and Barth Syndrome, a rare genetic disorder that can cause heart failure, muscle weakness and infection.

These diseases are among the 7,000 rare diseases affecting 25 million Americans. 

Kristen Steele hired a lawyer and filed a lawsuit in order to make her career dreams come true. Read her story here.

“Imagine the impact if we all get together and say, ‘We’re here! Twenty-five million people who can vote!’ ” said Booker, who works professionally and personally to help seek justice in the Philadelphia community.

Live long with advocacy

She co-founded the Young Adult Sickle Cell Alliance after her last hospitalization for SCD-related problems in 2012. Doctors with no answers asked what she usually did when symptoms occur, and she replied: “I thought I was here to get help from you.”

SCD is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body, according to the National Institutes of Health (NIH). People affected have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle or crescent shape.

“I’m talking about it every chance I get,” she said.

If someone notices she’s limping, she tells them she’s got sickle cell, a genetic disorder, “where a whole bunch of cells get together and attack your body, your heart, your eyes, your joints.”

“It’s about accommodating you and whatever it is you’re going through, to make it easier to function.”

Young people with SCD especially need to be empowered to speak up for what they need when they need it and Booker focuses on youth for a big reason: “As a child (with a rare disease), they love you. Once you become an adult, people don’t care about you anymore.”

She encouraged advocating for rare diseases by taking part in events surrounding Rare Disease Day, celebrated annually the last day of February. Rare Disease Week in Washington, D.C., and a multitude of events happen nationally and globally around that time.  

“Help sickle cell patients live long with advocacy,” she said.

The more members of Congress and state legislatures hear stories from rare disease patients and advocates, the more progress will be made toward funding research to find treatments and cures.

“Don’t be afraid,” Booker said. “No one can tell your story but you.”

‘Increase the volume’

Panel member Jill Dolgin, PharmD, Head of Patient Advocacy at Applied Genetic Technologies Corp. (AGTC), said rare diseases are small diseases, and suggested a way for people with rare disease to be heard above the noise of research news on more familiar diseases.

“I call it building an orchestra,” – talking about LCA, inherited retinal diseases (IRDs), blindness and genetic testing on the internet, in social media and at conferences – so you’re all “singing the same song” and constantly increasing the volume and frequency of the messages in the song. 

AGTC is developing genetic therapies to treat patients with rare inherited conditions, with its most advanced therapy programs designed to restore visual function and meet the needs of patients with rare blinding conditions, according to the company’s website.

Dr. Dolgin, a healthcare professional with more than 20 years’ global experience in public policy and patient and professional advocacy, said she brings the voice of the patient to small- and medium-sized biotechs to ensure that the needs of the patient are considered and incorporated into every aspect of drug development.

“I’m really helping one patient, one family at a time.” 

‘Be involved’

Panelist Jamie Ring is Head of Patient Advocacy at Spark Therapeutics, developer of LUXTURNA™, the first approved drug in the United States and Europe to treat an inherited genetic disease and to treat the RPE65 gene which, when mutated, causes one of the more than 25 forms of LCA. She previously worked at Genzyme, a Sanofi company, where she led rare disease patient advocacy and humanitarian programs. 

Ring said her role at Spark Therapeutics is three-fold. 

She serves as a liaison between the company and rare disease communities: “Serving as the voice of the patient inside the walls of our organization.”

She hears directly from the community: “At Spark, it’s really critical for us to understand what the needs of the patients are. You all have a voice at that table.”

Ring also helps connect different rare diseases together to learn how they develop and progress.

LUXTURNA came to fruition after 12 years of research and more that $500 million in investment. The U.S. Food and Drug Administration gave its approval in December 2017. 

“Be involved,” Ring advised the gathering. “Understanding what matters to you, matters to us.”

Panelist Emily Milligan, Executive Director of the Barth Syndrome Foundation, said she is socially and medically committed to serving underserved populations. Before leading the foundation, she launched an $80 million venture fund developing products for Type 1 diabetes and worked with the Juvenile Diabetes Research Foundation overseeing an annual $100 million research portfolio.

Barth Syndrome primarily affects boys and is a multiple-system, complex disorder caused by a chromosomal mutation. It can cause growth delay, impaired lipid metabolism and extreme fatigue. Severe symptoms can result in needing a heart transplant, contracting potentially lethal infections and even death.  

The syndrome, Milligan said, can turn a scraped knee into a trip to the emergency room with sepsis, a life-threatening condition occurring when the body cannot fight infection.

The foundation, she said, became the 14th organization to host a high-level meeting with the FDA, where more than 25 percent of the Barth community, which is about 250 worldwide, told their stories. In research, a second clinical trial is underway toward changing the biology associated with Barth that could mean an improved quality of life for some.

“You have to come together,” Milligan told the group. 

This family conference in Philadelphia has such an enormous impact when people gather together for a common goal, she said. 

“You have no idea the power in numbers. You are a community.”

Kristen Steele: You’ve Gotta Fight for Your Right …

Kristen Steele knows a thing or two about telling her story and getting what she needs to be her best.

The 22-year-old from Council Bluffs, Iowa, is a licensed massage therapist in Iowa and Nebraska. She travels throughout rural Nebraska, giving massages to the elderly and the ill as an independent contractor specializing in geriatric care.

But she had to fight to take her massage therapy exam in Braille. Never had anyone taken the Massage and Bodywork Licensing Examination, known as the MBLEx, in Braille.

Kristen told her story to people living with Leber congenital amaurosis and other inherited retinal diseases (IRDs) at the Hope in Focus (formally Sofia Sees Hope) second LCA Family Conference in Philadelphia in July. The gathering brought together patients, advocates, doctors, researchers and biotechnology leaders – more than 80 people from across the nation and Mexico. She spoke from the audience following the conference’s session on patient advocacy called “Your Voice Matters!”

Doctors diagnosed Kristen with LCA as an infant, while her clinical diagnosis of LCA10 (CEP290) came years later in middle school. She learned Braille at age 3.

Kristen planned to be an English teacher but decided her passions aligned more with the medical field. She enrolled in Midwest School of Massage near Omaha after rejecting another school because of difficulty accessing its curricula. At Midwest, she found an instructor with a background in exercise physiology and physical therapy. She said the teacher cared and put in extra time to make sure she fully understood the techniques.

After completing the 1,000-hour massage therapy course on anatomy, physiology and pathology, plus 200 practice massages, with a 4.0 average, Kristen learned she couldn’t take the exam in Braille. Instead, volunteer readers administered the test to people with visual impairment. Readers could be unfamiliar with and prone to mispronouncing complex anatomical and medical terms, putting Kristen at risk of failing the exam. Plus, she didn’t want to pay the $195 exam fee twice. 

She found a blind lawyer in Iowa and they sued the Federation of State Massage Therapy Boards. She reached a settlement agreement and took the exam, passing on her first try. Kristen also insisted on having a professional reader, an occupational therapist familiar with terminology used in the test questions – just in case she needed clarification.

Kristen polished her resumé with the help of visual interpreter services, highlighting her certificates in advanced dementia processes and other therapies.

“It placed my disability on the back burner, and it gave me the upper hand when you have sighted massage therapists and they’re interviewing without any of these advanced certificates,” she said.

A company interviewed Kristen by phone last year and hired her the day after her in-person interview. She continues to thrive there as a massage therapist specializing in geriatric care. She also devised her own transportation system to get to and from clients in the Nebraska countryside. 

Kristen paved the way for others, including perhaps another conference attendee, Danielle Senick from Norwich, Conn. Danielle is studying to be a massage therapist, and Kristen said she will be there to help her succeed in changing the rules to take the exam in Braille in Connecticut.

Dr. Jean Bennett: ‘Seeing the Light with Retinal Gene Therapy’

Known as a pioneer in gene therapy, Jean Bennett, MD, PhD, surveyed her audience of patients and families living with Leber congenital amaurosis and declared: “YOU are all the pioneers!”

Dr. Bennett, addressing more than 80 people from 15 states and Mexico at the Hope in Focus (formally Sofia Sees Hope) second LCA Family Conference, characterized the meeting as a great place to reach out to patients to participate in clinical trials. Researchers normally recruit study patients through advertising.

Along with families living with LCA and other inherited retinal diseases (IRDs), people attending the summer conference in Philadelphia included patient advocates, doctors, researchers and biotechnology industry leaders.

Dr. Bennett is Professor of Ophthalmology at the Center for Advanced Retinal and Ocular Therapeutics and the F.M. Kirby Center for Molecular Ophthalmology at the Perelman School of Medicine, University of Pennsylvania. She gave her presentation as part of a conference session called “One Disease, Many Approaches.”

Viral Vectors Key 

Dr. Bennett was one of the first investigators to use viral vectors, in which a virus is used as a vector or carrier that is genetically engineered to deliver the gene to specific cells in the retina.

Lancelot, a golden colored dog standing on the steps with the U.S. Capital behind him
Lancelot on steps of the U.S. Capitol.

She emphasized that LUXTURNA™, the breakthrough genetic treatment she and her colleagues developed at Children’s Hospital of Philadelphia (CHOP) and Spark Therapeutics, began with the successful treatment of a special being: Lancelot, the first in a line of Briard herding dogs, who helped drive research to bring to market gene therapy that improved vision by focusing on a particular mutated gene.

Dr. Bennett and her colleagues studied Lancelot and the other dogs after learning that a veterinary ophthalmologist had identified the gene which, when mutated, led to blindness in Swedish Briard dogs. 

The research dogs received an engineered virus delivering the human RPE65 gene, a gene that, when mutated, causes LCA RPE65, also known as LCA2, one of the more than 25 forms of LCA. Doctors delivered the drug by subretinal injection through a needle the size of an eyelash. The treatment works by encoding an enzyme that converts light into electrical signals interpreted by the brain.

Dr. Bennett’s presentation, “Seeing the Light with Retinal Gene Therapy: From Fantasy to Reality,” features a photograph of Lancelot wearing glasses and perusing his article in Nature Genetics magazine. 

Lancelot accompanied her on her frequent Congressional visits to lobby for more research funding. Dr. Bennett said Lancelot’s distant cousin, Venus, and later her pups, Mercury and Saturn, also successfully received the treatment. 

According to an article in the Philadelphia Inquirer, “Before the treatment, Venus preferred to crouch in a corner for fear of bumping into objects. But after the treatment, it was clear that Venus and the other dogs were able to see. They could easily navigate obstacle courses set up by researchers. Venus was a new dog, eager to walk around and explore grass, birds, and squirrels for the first time.”

Dr. Bennett, noting Venus’ recent passing, said, “She died of old age. Still seeing.” The headline on Venus’ July 16 obituary in the Philadelphia Inquirer read: “Main Line dog, used to help cure blindness in humans, dies at 12.”

First Dogs, Then People

The trials on dogs led to successful treatment in people beginning in 2007 after Dr. Bennett and her husband, Dr. Albert Maguire, teamed up with Dr. Katherine High to run human clinical trials. Christian Guardino, an America’s Got Talent Golden Buzzer award winner from Long Island, received treatment at age 13 during the trials, as well as others, including Cleveland-area resident Tami Morehouse, who at age 44 at the time, was the oldest participant in the trial. 

LUXTURNA, approved by the U.S. Food and Drug Administration in December 2017, is the first and only approved gene therapy for inherited disease in the United States and Europe. The breakthrough medicine unlocked the potential of the Human Genome Project to provide options for people when there were none.

The treatment fostered pioneering changes in medical practices, motivating ophthalmologists and insurers to do genetic testing, and it created a path for genetic treatments to blindness.

Dr. Bennett said she is thankful for the clinical trial participants, team members, regulatory bodies, advisors and the dogs who helped along the way.

Genetic research still faces a host of challenges, including the rapid degeneration of cells needed for gene therapy to work and too long a span of time to get results for diseases that progress very slowly.

More patients have been treated with LUXTURNA post-FDA approval than the 29 who received treatment during the trials. In the first few months after approval, more than a dozen people underwent treatment at CHOP, one of the 10 approved treatment centers in the United States. Also, the first patient in Paris received the gene therapy in January.

Successes with the New Treatment

'Retinal Gene Therapy is Alive and Well' slide

Before LUXTURNA, no path existed for pediatric drug development in ophthalmology. In a slide titled “Retinal Gene Therapy is Alive & Well,” Dr. Bennett said more than 700 people are enrolled in clinical trials at more than 30 sites. 

“We obtained approval and paved the way for all future pediatric gene therapy trials,” she said. 

As this genetic superhero said at the beginning of her presentation – that the audience members are the pioneers – Dr. Bennett looked out at the gathering as she ended her talk and declared: “It is the families who are really the heroes.”

Explosive Growth Seen in Field of Rare Inherited Retinal Disease Research

Advances in genetic sequencing boosted research into rare inherited retinal diseases (IRDs), making a tremendous impact on the number of clinical trials underway for genetic treatments.

“There are 37 trials in IRDs; 10 years ago, you could count them on your fingers,” said Foundation Fighting Blindness Chief Executive Officer Benjamin Yerxa, Ph.D. 

Also, genetic testing zoomed from zero-possibility to an individual being able to receive a full genetic sequence within a few weeks for a couple of thousand dollars.

Dr. Ben Yerxa presenting
Dr. Ben Yerxa at the LCA Family Conference in July.

Dr. Yerxa opened the Hope in Focus (formally Sofia Sees Hope) second LCA Family Conference on July 27 in Philadelphia before an audience of more than 80 people from 15 states and Mexico. They represented patients and families living with Leber congenital amaurosis (LCA), other rare diseases (retinal and otherwise), and advocates, doctors, researchers and biotech leaders. 

He delivered updates on the Foundation’s work in his presentation, “Accelerating Translation of New Treatments for IRDs – A Foundation’s Perspective.” The Foundation, the world’s largest private funding source for research into treatments and cures for IRDs, has raised more than $750 million toward its mission since its founding in 1971. Sofia Sees Hope partners with the Foundation by helping provide families with free access to genetic testing, and funding research.

Advances in genetic sequencing

Dr. Yerxa credited the Human Genome Project (HGP) – costing an inflation-adjusted $5 billion – with netting continued advances in genetic sequencing and making great gains in the IRD field.

Researchers have identified the mutated genes in 65 percent of people with retinal disease who get genetically tested, and in 2017, the U.S. Food and Drug Administration approved LUXTURNA™, the first approved gene therapy for the eye or an inherited condition. LUXTURNA is for people with mutations in the RPE65 gene, one of the more than 25 genes that, when mutated, can lead to LCA.

Dr. Yerxa said that approximately 200,000 people in the United States have an IRD, with each condition meeting the definition of an orphan disease. 

'LCA By The Numbers' slide from 2019 LCA Family Conference

He also delineated the LCA trials in progress in an “LCA by the Numbers” presentation. He discussed an emerging treatment for CEP290 (LCA10) by ProQR, which is in a Phase 2/3 clinical trial, and research also on CEP290 by Editas Medicine and Allergan, who are recruiting patients in a landmark clinical trial to test a gene-editing technique called CRISPR/Cas9.

“We all know it takes a village,” Dr. Yerxa said. “There are tons of people involved in these programs.”

Supporting retinal research

'Innovation in Venture Philanthropy: RD Fund' slide

He also detailed the Foundation’s new “Innovation in Venture Philanthropy: RD Fund,” a first-of-a-kind retinal degeneration fund focused on IRDs. It is an internal venture philanthropy investment account overseen by an independent board of directors. Donor dollars go to biotechnology companies as investments, with financial returns reinvested to support the Foundation’s mission. 

Among its contributions to research, the Foundation gave $10 million toward the development of LUXTURNA and $6 million to the Natural History of the Progression of Atrophy Secondary to Stargardt Disease or ProgStar studies that produced new knowledge and potential outcome measures. 

Dr. Yerxa also reported impressive gains in membership to My Retina Tracker® (MRT), the free and secure online international patient registry managed by the Foundation.

“I call it the LUXTURNA effect. Thanks to LUXTURNA, registration went up like a hockey stick.”

With membership at more than 23,000 and growing, the registry’s goal is to drive research toward prevention, treatments and cures for people living with Retinitis Pigmentosa (RP), Stargardt disease, Usher syndrome and the whole spectrum of inherited retinal degenerative diseases, including LCA.

50 logos showing the involvement of biotechs in vision research

In a slide titled “Our Space is Very Active” showing a collage of more than 50 logos of biotech companies involved with vision research, Dr. Yerxa said, “More and more people are jumping into this space. 

“This is good news. Ocular is hot.”

Human Genome Project: Critical to Modern Gene Therapy Success

The long and sometimes uncompromising road to completing the Human Genome Project (HGP) paved the way for today’s surge in genetic therapy, Dr. Katherine A. High said in her presentation at the second Hope in Focus (formally Sofia See’s Hope) LCA Family Conference.

“It was a tremendous achievement,” Dr. High said, “And it forms an important bedrock for everything we are trying to do in gene therapy.”

The HGP began in 1990 with an international, collaborative quest to map and understand all the genes of human beings and their roles in health and disease. The project, completed in 2003, revealed that there are probably about 20,500 human genes, referred to collectively as our genome, according to the National Human Genome Research Institute (NHGRI).

Dr. Katherine High and Laura Manfre next to a Welcome poster
Dr. Katherine High and Sofia Sees Hope co-co-founder Laura Manfre at the LCA Family Conference in July.

Dr. High, keynote speaker and accomplished hematologist with a longstanding interest in gene therapy for genetic disease, kicked off the July 27 conference in Philadelphia.

More than 80 patients, family members, advocates, doctors, researchers and biotech industry leaders from 15 states and Mexico gathered for exchanges of knowledge and ideas about Leber congenital amaurosis, inherited retinal diseases (IRD) and other rare diseases. The conference grew out of the Sofia Sees Hope Family Connections program that brings together families living with LCA and other IRDs in a supportive community to help alleviate feelings of isolation that often come with a rare-disease diagnosis. 

Dr. High and her team at Children’s Hospital of Philadelphia (CHOP), including Dr. Jean Bennett and Dr. Albert Maguire, developed – from clinical trials to regulatory approval – the first gene therapy for any inherited genetic disease in the United States; it also is the first genetic therapy targeting a retinal disease worldwide. The treatment focused on LCA caused by mutations in the gene RPE65, one of the more than 25 different genes, that, when mutated, can lead to LCA.

‘The Long & Winding Road’

Spark Therapeutics, a company that spun off the team’s research at CHOP, developed the therapy called LUXTURNA™ after 12 years of research and more than $500 million in investment. The U.S. Food and Drug Administration (FDA) approved the human-engineered, injectable drug in December 2017. Beginning in 2018, patients with low vision caused by LCA-RPE65 underwent surgery to help improve their eyesight. 

LUXTURNA and the dozens of clinical trials now underway for retinal disease would not be possible if not for the HGP. Dr. High, Spark’s president and head of research and development, elaborated on the genome project in her presentation, “The Long and Winding Road: How the Human Genome Project and Gene Therapy Research Led to the First Gene Therapies for Genetic Disease.”

The ultimate product of the HGP – detailed information about the structure, organization and function of the complete set of human genes – can be thought of as the basic set of inheritable instructions for the development and function of a human being, according to NHGRI information.

Dr. High said the burden of genetic disease falls heavily on children’s hospitals, with 25 million Americans having a rare genetic disease. 

A 4-year-old made genetic history after receiving the first genetic transfer in the United States in 1990, leading eventually to licensing of a product for the same disease in Europe in 2016. But that span of time did not represent an unbroken chain of successes, Dr. High said. “Instead, it was punctuated by a number of adverse events and failed results.”

Rocky road to success

A teenager died in a 1999 genetic trial in Philadelphia, and in 2003, children in a Parisian clinical trial developed leukemia. 

A Wall Street Journal article about Spark Therapeutics

“Gene therapy was just not ready for prime time and there was a decline in trials and participation.”

Headlines such as “Gene Therapy Still Lacks Breakthrough” and “Gene Therapy: cursed or inching toward credibility” mirrored waning interest from pharmaceutical companies and investors.

Instead, the American and European Societies of Gene and Cell Therapy, the National Institutes of Health (NIH), of which the National Human Genome Research Institute is part, and academic medical centers, like CHOP and its Center for Cellular & Molecular Therapeutics, sustained genetic therapy research through rough times, allowing investigators to develop therapeutics based on best science, not commercial considerations, Dr. High said.

Investing in the RPE65 blindness clinical trials during this time ultimately led to the development and FDA approval of LUXTURNA.

“The ability to work through those adverse events brought us to where we are now,” she said.

An ‘extraordinary’ level of activity

In the United States, the clinical development phase of a drug begins when a sponsor files an Investigational New Drug application (IND) with the FDA. IND submissions with gene therapy products went from zero in 1963, to three in 1990, to more than 100 in 2017. Following LUXTURNA’s market entrance in 2018, sponsors submitted more than 200 INDs.

“The level of activity in the last few years is truly extraordinary. It’s a very compelling statement of how people are investing time and energy into gene therapy,” which High said is probably the most complicated treatment researchers have tried to develop.

“It’s a complex therapeutic. The outside is a protein. The inside is a piece of DNA and those things have to be assembled in the exact proportions or it’s not going to work right.”

Dr. High also described the increased progression of identifying genes involved with vision – from zero in 1980 to more than 300 by January 2019. 

“It’s daunting to think about the number of development programs that might need to be initiated and taken all the way through. But a journey of a thousand miles begins with a single step.”