The rare disease causes hearing loss, balance problems, difficulty with gaze stabilization, and progressive vision loss. In childhood or by early adolescence, individuals with USH1F will develop retinitis pigmentosa (RP), an eye disease that causes night blindness and a gradual loss of peripheral vision.
“The main purpose of a study like this is to help design clinical trials in the hopes of accelerating the research process, making sure the design is well-targeted, not too onerous and not too burdensome,” said Todd Durham, Foundation Vice President of Clinical & Outcomes Research. He described the study during a recent Sofia Sees Hope webinar about the Foundation’s My Retina Tracker® patient registry.
“If we can develop a way to measure the progress of the disease in the absence of a treatment, we can decide whether the follow-up period after administration of that treatment should be two years, would one year suffice, and what tools do we ultimately judge the efficacy of that new treatment.”
Joseph F. Smith has been legally blind since birth. He lost what little sight he had in his mid-30s, when he learned he had Leber congenital amaurosis (LCA). Thirty years later, genetic testing revealed a mutation in his CRB1 gene, a diagnosis known as LCA8.
More than 40 leading experts in ophthalmology and gene research gathered virtually for more than five hours in February to share research and patient perspectives on CRB1 and identify the next steps to advance treatment for the patient community.
The CRB1 gene provides the body with instructions for making a protein that plays an essential role in normal vision. This protein is found in the brain and the retina, which is the specialized tissue at the back of the eye that detects light and color.
Alice and Joe
While the biology for CRB1 is particularly complex, early research produced the discovery of a new version, or isoform, called CRB1b. Preclinical studies give rise to new questions as to whether CRB1a or CRB1b expression, or both, should be the target of a gene therapy. Click here to view the webinar.
In his letter, Joe wrote: “I won the CRB1 lottery 76 years ago and spoke briefly during the webinar.”
When we spoke to Joe by phone, he wanted to know what he could do to reassure parents of children who are blind or visually impaired that they can thrive.
Joe earned a law degree from Cornell Law School after graduating as a math major at Alfred University in upstate New York. He worked at the New York City Corporation Counsel’s Office in the Real Estate Tax Division for three years.
While working, Joe began his teaching career at New York’s Dominican College where he taught a business law course. He taught law at the University of Baltimore Law School in 1973, and three years later accepted a job at Fort Lauderdale’s Nova Southeastern University School of Law, where he became a tenured professor and taught for more than 30 years.
He is retired, living in Florida with his wife of 51 years, Alice.
The Importance of Learning Braille
Joe’s 76-year journey began long before the enactment of the Individuals with Disabilities Education Act and the Americans with Disabilities Act, Congressional civil rights legislation prohibiting discrimination and guaranteeing that people with disabilities would have the same opportunities as everyone else. He said he was fortunate to receive scholarships from an earlier version of the Rehabilitation Act of 1973 to fund his higher education.
People with vision difficulty or other challenges must still vigorously advocate for accessibility and equality, but those roads were even bumpier in the past.
Before retiring, Joe developed a course on the rights of people with disabilities. He also created a program in which he supervised students working for organizations providing services for people with disabilities.
He understands that ever-evolving technology greatly helps people with vision loss, but he is a proponent of learning braille.
“One thing I do think is very important is that a child who is losing sight or is blind needs to learn braille. I know many educators will say with accessible computers, cell phones, and recorded materials, braille is unnecessary. My simple response is, ‘All that technology is available to sighted people, but they still use pens and pencils.’
“If you learn braille, you have something to keep in your mind. You have a physical image of the written word.”
With CRB1, Supportive Parents and Friends
Joe believes much of the credit for his success goes to his blue-collar parents who did not graduate from high school.
“I can’t imagine what it must have been like for them to find out I was blind and with no explanation as to why.”
Early on he could distinguish basic colors and he can still see red and orange in his mind’s eye.
Growing up in the 1950s, “back in the dark ages,” Joe said his parents knew that the local Catholic school was not going to work for him because it offered no resources. His mother wanted to wait a year for him to go to first grade, but his father said no. A learning disability kept Joe’s dad back a year because he could not read, prompting him to quit school in eighth grade to play baseball.
“He knew that education was important.”
Joe attended Lavelle School for the Blind run by Dominican nuns in the Bronx, leaving home Sunday nights and returning Friday afternoons, through eighth grade.
Lavelle served Joe well, but he wanted to attend a regular high school – any school that would take him, as mainstreaming was not a big goal back then and schools were not obligated to accept students who were blind.
He went to Archbishop Stepinac High School in White Plains run by the Archdiocese of New York. His senior year, another blind student was accepted to the school.
Math books in braille were in short supply and books in general were hard to get, so his mom read to him – a lot.
His dad also rarely said no to him trying new things. He rode around the neighborhood on his bike, enjoyed daredevil sledding, and loved cars in high school. His dad took him to an empty parking lot and taught him how to drive a stick-shift.
But the pièce de resistance for this self-described car nut came when he slid behind the wheel of an automatic BMW for the ride of his life on the skidpad at a defensive driving school.
“Truth be told, my wife was taking the course, but the instructors snuck me out for an unforgettable hour of bliss.”
I guess what I’m trying to say is a child who is blind should be encouraged to develop interests in and to try activities, which, at first blush, might not seem suitable for a child with limited or no sight.
His best friend in grammar school read him comic books, and as they got older, car magazines. They didn’t go to the same school, but they managed to get into trouble together and often double dated.
He excelled in math and thought he might be an engineer, toyed with psychology, and after Alfred University, decided to go to law school.
Practicing and Teaching Law
Joe met Alice on a blind date in his second year of law school when she was a sophomore at New York’s Wells College. She earned a Bachelor of Arts and worked in the Criminal Division of the Legal Aid Society of Westchester County while pursuing her master’s degree in early childhood education at Manhattanville College. They married in 1970.
Joe did well in law school and said he knew if he were not blind, he would have received more than one job offer after graduation. He received many rejection letters, heard many excuses, and sometimes heard nothing at all after interviews.
Still, he almost did not interview for that one job offer; only after repeated urgings from different people, he did so and got the job at New York City’s Corporation Counsel’s Office, which already employed a blind lawyer in the Real Estate Tax Division.
Recounting his getting the job despite almost not interviewing, Joe invoked an ancient adage: “Luck is what happens when preparation meets opportunity,” words from Roman philosopher Seneca, reminding us that we make our own luck.
After three years of practicing tax law, Joe wanted to try something else, perhaps be a trial lawyer or a teacher. He and Alice drove out to Colorado where he planned to take the Colorado bar exam, but the day after they arrived, he was offered a teaching job at the University of Baltimore.
Before returning East, he and Alice goofed off and he learned how to ski, loving the feeling of freedom, and losing his fear of speeding down a mountain.
When they moved to Baltimore, Alice, who worked at the Baltimore Museum of Art, read for Joe from textbooks.
“Most importantly, from that time until I retired from teaching in 2007, she read all of my exams and papers to me.”
Getting a Confirmed CRB1 Genetic Diagnosis
Joe was diagnosed in his late 20s with retinitis pigmentosa (RP), but he thought it wasn’t correct for several reasons, including that people with RP lose peripheral vision and, in his case, he lost central vision.
Joe and Alice met Gordon and Lulie Gund while learning to ski at Snowmass in Colorado. The Gunds co-founded Foundation Fighting Blindness in 1971 to fund research for treatments and cures for blinding retinal diseases after Gordon was diagnosed with RP and ultimately lost his vision in 1970. He is a Foundation director and chairman emeritus.
Gordon came back into Joe’s life in the 1990s when he invited him to a Foundation dinner. There he met Iowa State University’s Edwin Stone, MD, PhD, who spoke of emerging research into gene therapy targeting a form of LCA and suggested Joe get genetically tested.
Joe and Alice
Joe’s genetic test showed his LCA was due do a mutation in his CRB1 gene, not the RPE65 gene, the focus of the research that led to the 2017 federal approval of LUXTURNA®, the first gene therapy for the eye or an inherited condition. People with LCA2 (RPE65) cannot make a protein needed by the retina to convert light into vision-enabling signals, which are sent to the brain. The breakthrough therapy involves injecting under the retina a human-engineered virus containing copies of a normal gene, so cells can express the protein.
In the CRB1 Research Update webinar, Joe said he was fortunate to have lived near a teaching hospital where he could learn about the cause of his blindness. In the Q&A, he asked where people with visual impairment should turn for help when living in rural areas with less accessibility to universities or large hospitals.
In answer, Ben Shaberman, Senior Director of Scientific Outreach and Community Engagement for the Foundation, said a team is working nationwide to educate eye-care professionals about LCA and other rare inherited retinal diseases (IRDs), so they can refer patients to specialists. He also encouraged people to email the Foundation at info@fightingblindness.org for contacts in the academic and medical worlds of retinal specialists and researchers.
Laura Manfre, Sofia Sees Hope Co-Founder and President, said people can follow the Foundation and Sofia Sees Hope websites for information and research news. They also can email their questions and concerns to info@sofiaseeshope.org.
As a lawyer, a law professor and a man diagnosed only a decade ago with CRB1, Joe said, “I’m not trying to paint an overly rosy picture of the challenges we face. I realize I am a minority, as I’ve been employed continuously from law school graduation to retirement. I also know with my class rank, I should have had more than just one job offer coming out of law school. At the same time, I realize that technology that was not available to me then has opened up many more opportunities for us …
“I guess what I’m trying to say is a child who is blind should be encouraged to develop interests in and to try activities, which, at first blush, might not seem suitable for a child with limited or no sight.”
Early research into a form of Leber congenital amaurosis (LCA) caused by mutations in the CRB1 gene – including the discovery of a new version of a protein expressed by the gene – shows encouraging possibilities toward developing gene therapy treatment.
Amy Laster, PhD, Vice President of Science and Awards programs for the Foundation Fighting Blindness, shared the research news as part of a recent LCA Research Update webinar, summarizing results of an earlier CRB1-associated retinal disease Scientific Advancement Workshop.
“There’s certainly momentum that the research is actively happening, and that the community wants to address outstanding issues,” Laster said.
Laura Manfre, Sofia Sees Hope Co-Founder and President, said more than 40 leading experts in ophthalmology and gene research gathered in one room for more than five hours to share research and patient perspectives on LCA8 (CRB1) and identify the next steps to advance treatment for the patient community.
Sofia Sees Hope and the Foundation Fighting Blindness created the Scientific Advancement Workshop with the objectives of widening the circle of research awareness into CRB1, building a framework or platform for sharing knowledge, fostering collaboration among stakeholders, identifying gaps, and setting priorities for action.
The route to approved LCA treatments consists of multiple, winding paths rather than one direct straightaway: No quick, easy solutions.
“For CRB1, in particular, the biology here is very, very complex,” said Manfre, who is also a member of the Foundation’s Board of Directors.
Referencing results of the workshop, Manfre displayed what she called a “celebration photo” of a smiling young girl hitting a piñata bursting forth with sprays of candy.
“What I want to communicate here is just how much of a celebration it is that we had this workshop. There are no simple, straightforward answers, but the really good news, or the celebration, is that this was one more step ahead in bringing the right people and all the very smart people together,” Manfre said.
CRB1 Preclinical Research
Laster described the gene therapy development path from research to treatment or cure. The path begins with basic knowledge of the gene and its functions and understanding the biology of the disease, which includes designing non-human research models and conducting Natural History studies.
Preclinical CRB1 research currently centers on understanding the biology of the mutation and working toward conducting a Natural History study.
Natural History study researchers observe clinical features in the absence of any treatment, gaining an understanding of myriad features, including the retina’s architecture and the patient’s visual function, sensitivity to light, and peripheral vision. The data provide knowledge and an independent understanding of the disease, while establishing an essential foundation for building drug development programs.
Later stages on the way to treatments and cures include designing clinical trials, selecting patients, predicting outcomes, setting measures for endpoints and outcomes, and conducting Phase I, II and III human clinical trials. The goal is U.S. Food and Drug Administration approval of a safe and effective treatment.
Laster shared news from the workshop that Jeremy Kay, PhD, found a new version, or isoform, of CRB1 called CRB1b.
Kay, Associate Professor of Neurobiology and of Ophthalmology at Duke University, found that the CRB1b protein is more abundant in human and mouse retinas than the first identified version, CRB1a.
“Unlike CRB1a,” Laster said, “the removal of the CRB1b causes a retinal degeneration in mice and this has not been shown before with the first identified isoform.”
The research gives rise to new questions as to whether CRB1a or CRB1b protein expression or both should be the target for a gene therapy, she said.
Duke University research news characterized Kay’s findings published in Natural Communications as “a game-changer in light of the critical progress, over the past few years, in the treatment of inherited retinal diseases …”
Laster referenced CRB1 research models and gene augmentation therapy studies by Jan Wijnholds, PhD, Principal Investigator in the Department of Ophthalmology at Leiden University Medical Center, Leiden, Netherlands. The findings by him and his team can be found here in Frontiers in Neuroscience.
She also discussed the work of Dr. Jacque Duncan, Professor of Clinical Ophthalmology at the University of California, San Francisco. Dr. Duncan is in talks with the Foundation about her interest in understanding the relationship between CRB1’s genotype and phenotype, or its genetic characteristics and physical characteristics.
“On the clinical side, in terms of actually conducting a Natural History study, there was a lot of enthusiasm about that,” she said. “The Foundation is in touch with Dr. Jacque Duncan about potentially moving forward with that.”
The Foundation, the largest private funder of research for treatments and cures of blinding retinal diseases, has raised nearly $800 million since its inception and funds more than 80 research projects globally. Laster oversees the organization’s preclinical research portfolio consisting of research awards in funding programs that support career development, laboratory-based science research, translational research, and multi-investigator program projects.
CRB1 Patient and Caregiver Survey
Todd Durham, PhD, also an organizer of the Scientific Advancement Workshop, said sharing CRB1 patient perspectives through survey answers marked one of the highlights of the workshop because it gave researchers insight to help focus their studies for treatments or cures.
In the survey developed by the Foundation Fighting Blindness and Sofia Sees Hope, 85 percent of the respondents have a profile on My Retina Tracker® registry, a free online registry that enables people with inherited retinal degenerative diseases, their doctors, and researchers to actively collaborate in the research process.
Durham, the Foundation’s Vice President of Clinical and Outcomes Research, said the CRB1 survey also showed patients received a clinical diagnosis at an average age of 13, while 24 was the average age for getting genetically diagnosed, showing a significant gap between the diagnoses.
The most reported worries were progression to blindness and concerns about employment. Most of the survey takers said they would participate in clinical trials, while many were concerned about the safety of the trials, the risks to remaining vision, and the potential for benefit.
People also were asked to describe their motivation for taking part in a clinical trial. A common thread to the responses, Durham said, was to help themselves see better and help others through research.
In a sampling of comments, one person wrote: “1. Cure the disease. 2. Have a more comfortable life. 3. Not feel different from the rest because of your visual impairment.”
Under the section “Anything Else to Share with Researchers,” a respondent wrote: “I feel the mental health impacts of a disability are overlooked a lot of the time.”
An Engaged CRB1 Community
In the question-and-answer session, an audience member asked where to go for information about CRB1, noting that his doctor had no idea about it. He said he felt lucky to live near a teaching hospital and could reach out for help but thought others may not be as fortunate.
Ben Shaberman, the Foundation’s Senior Director of Scientific Outreach and Community Engagement, said he understands that difficulty and he is part of a team educating eye-care professionals around the country. He encouraged people to email the Foundation at info@fightingblindness.org for contacts in the academic and medical world of retinal specialists and researchers.
Manfre said the CRB1 community is highly active and suggested that people join the new CRB1 Network on Facebook and check out the Resources page on the Sofia Sees Hope website that has a link to a CRB1 group called Curing Retinal Blindness Foundation. She said people can also find a strong Spanish-speaking community at Grupo CRB1 España y Latinoamérica.
She advised people to update their profiles on My Retina Tracker to help advance research and to follow the Foundation and Sofia Sees Hope websites for information and research news. You can email questions or concerns to Sofia Sees Hope at info@sofiaseeshope.org
Advocating for treatment and cures for rare diseases such as CRB1 takes a grassroots effort, Manfre said, requiring people to inform, support, and educate one another, and to continue sharing stories and reaching out on social media.
Gathering in groups such as this webinar, she said, also helps connect people and generate awareness that, in turn, advances research.
Welcome to the Sofia Sees Hope Scavenger Hunt! We are glad to meet you.
We are doing this to continue to raise awareness for rare inherited retinal disease and Leber congenital amaurosis, which is challenging during a global viral pandemic. We launched it last year because of the coronavirus crisis, when in-person fundraising went dark and we were unable to be with our family and friends in person. It was so fun that we are bringing it back this year, even as COVID restrictions are being lifted in many places. As always, we ask that you adhere to your local requirements, and practice social distancing and mask wearing where required or prudent.
Your entry fee will benefit Sofia Sees Hope, and the education, outreach and advocacy work we are engaged in. We will also make a donation from the entry fees to a 501(c)3 nonprofit of the winner’s choosing (up to $250)! This way you can help a charity in your community that is also doing important work.
The Scavenger Hunt is open to anyone around the world! The maximum number you can have on your team is 5 (five) but they don’t all have to live in the same house! This could be a fun way to stay in touch with friends or family.
The only equipment you’ll need is a smart phone that can take photos/videos and a Facebook account.
To be officially entered, you must fill out this Google form. Once we receive your entry, you will be emailed confirmation and a link to make your suggested minimum team donation of $100. (Here’s the official rules, etc. you need to know.)
The Scavenger Hunt runs from Friday, May 21 through Monday, May 31. On opening day, you will receive an email with the list of challenges. You must complete 10 (ten) of the challenges by 11:59 p.m. EST Monday, May 31 to be entered into the pool to win.
There will be 2 additional requirements in the game:
To begin, at least ONE member of each team must complete a quiz about rare disease. You will receive a link to the quiz in the confirmation email.
On the last day, Wednesday, May 20, at least ONE member of each team must share 3 facts about Leber congenital amaurosis or rare disease on their Facebook, Instagram or Twitter and tag Sofia Sees Hope (@sofiaseeshope on all platforms). It can be 3 facts included in 1 post, or 3 separate posts.
You will post all your photos and/or videos in this Facebook group as you complete challenges. Once you are confirmed as entered in the hunt, you will be invited to join the Facebook group. The group is private, meaning that no one outside it can see who is a member, or any of the posts.
And the winner is …
Every team that completes 10 challenges by the hunt’s end will be entered into a random drawing for the winner.
The winner will be able to designate a 501(c)3 nonprofit of his/her choosing to receive a donation from Sofia Sees Hope!
The winner will be announced Friday, June 4 in the Facebook group, on our public social media platforms, and notified by email.
Researcher Jonathan Stokes says he takes a holistic approach in developing and evaluating patient-health outcomes in clinical trials that include focusing on signs and symptoms of disease, health-related quality of life for patients, understanding unmet needs, and exploring the burden of disease.
“Patient voices matter,” he said.
Stokes is Director of Patient-Centered Outcomes Research for AbbVie, a Chicago-based biopharmaceutical company. He holds a Master’s in Business Administration from Northeastern University and has a devoted interest in understanding and bringing to light the patient voice and perspective, with more than 16 years of research study design and implementation experience.
He primarily works in health-outcomes research, specifically developing and evaluating clinical outcomes of assessments (COAs) used in clinical trials to substantiate treatment benefit.
Sofia Sees Hope featured Stokes in an April 19 webinar episode of “Let’s Chat About…Why natural history and patient outcome studies are important.” Elissa Bass, Director of Marketing and Communications for Sofia Sees Hope, moderated the session that is part of the organization’s free, monthly webseries.
We developed the series with the LCA and IRD communities in mind but invite all members of our community, including those in research, industry, and the regulatory communities to join any of the sessions as we look ahead to a common goal of advancing treatments for rare retinal disease.
Objective Versus Subjective Gauges
Patient-centered outcomes are evaluations of a patient’s health status and provide valuable information on how patients feel and function.
Vision measured by navigating a maze renders a tangible, objective result, as do blood tests that reveal cell counts or measures that evaluate tumor size in oncology.
Certain conditions, or aspects of a given condition, express themselves in ways only known to the patient, such as fatigue with mitochondrial diseases or pain with migraines. These subjective experiences can be assessed in studies and through outcome measures, such as daily diaries or questionnaires. These assessments involve years of qualitative and quantitative research, and they are designed after consulting with patients, their caregivers, doctors, researchers, and literature.
This information literally is the patient’s voice.
Stokes says, “For me, the question is always the ‘So what?’ What does that mean to the patient?’ ”
He takes an inclusive approach to developing measurements for patient outcomes, considering quality-of-life elements – the effects of a disease emotionally, socially, physically, and in daily activities – to produce valid, reliable results.
“Even if you are not taking part in a clinical trial, these are all steps that need to be done to make sure we’re doing it the right way.”
The information, in turn, is shared back with the patient community.
“These kinds of things matter to people,” he said. “Their feelings are not just idiosyncratic to themselves.”
This research is critical to the drug approval process and important to all stakeholders – patients, care givers, researchers, regulators, and drug developers – to create what Stokes calls a true partnership.
“PFDD is a systematic approach to help ensure that patients’ experiences, perspectives, needs, and priorities are captured and meaningfully incorporated into drug development and evaluations,” according to the FDA.
The goal is to better incorporate the patient’s voice in drug development and evaluation, which ultimately results in an FDA-published document called “Voice of the Patient.”
Long-term Tracking
Natural History studies also are important to patient outcomes because they reveal the patient experience over time as researchers observe features in the absence of any treatment. These data give knowledge and an independent understanding of the disease, while establishing an essential foundation for building drug development programs. A Natural History study also can be used as a control arm serving as a placebo in a clinical trial.
The studies track the course of a patient’s disease, identifying demographic, genetic, environmental, and other variables that shape the drug development process. They give scientists and researchers a better estimate of the prevalence of the disease, help identify biomarkers, affect clinical outcome assessments, and determine the feasibility of established assessments for clinical trials.
More than ever, Stokes said, all stakeholders in the drug development process come together and work toward a solution best for the patient.
You or your loved one just received a clinical diagnosis of Leber congenital amaurosis (LCA), a rare inherited retinal disorder caused by a mutated gene. The disease causes severe vision loss at birth and affects the peripheral rod cells that allow night vision and the central cone cells responsible for fine detail and color vision. What now?
The next most important step is to get a genetic test for a confirmed genetic diagnosis to clarify the underlying genetic explanation of the disease. Finding the specific gene causing the defect is critical for moving forward with research and treatment.
Genetic counselors like Emily Place help navigate the complex world of gene mutations, genetic testing, and genetic diagnoses. She is among the more than 4,700 certified genetic counselors nationwide, and she specializes in counseling families living with inherited retinal diseases (IRDs).
Place, a Licensed Genetic Counselor and Research Study Coordinator at Massachusetts Eye and Ear (MEE), discussed her role in the ever-evolving world of genetics in our March webinar episode: “Let’s Chat About…the ins and outs of genetic testing.” Sofia Sees Hope Director of Marketing and Communications Elissa Bass moderated the monthly series, which you can watch here.
Place began her work at MEE’s Ocular Genomics Institute (OGI) in 2011, about the same time the first clinical trials were underway for a vision-improving gene therapy. Six years later, researchers identified, and regulators approved LUXTURNA®, the first gene therapy treatment for an inherited disease, and specifically for LCA2-RPE65, one of the more than 25 gene mutations associated with LCA.
She earned a Bachelor of Arts in Biology from the University of St. Thomas and her master’s degree in Human Genetics from New York’s Sarah Lawrence College, which in 1969 established the first graduate degree program in genetic counseling. With ever-expanding genetic studies, the profession dramatically increased with more than 50 programs now in the United States.
Basic Genetics
The Human Genome Project (HGP) began in 1990 as 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 there are probably about 20,500 human genes, referred to collectively as our genome, according to the National Human Genome Research Institute.
Scientists have since identified more than 30,000 genes in our body and more genetic causes of inherited conditions, and more research remains to be done to better understand the causes of inherited conditions and to identify more genes.
“Genes are instructions or blueprints that tell us how to grow and function,” Place said.
This genetic information is organized in our chromosomes and can be found in every cell of our body.
More than 200 genes have been identified as playing a specific role to help retina function.
“These inherited retinal conditions can arise because of a genetic variation or change within a gene that we know is important for retinal function and, what we really mean here, is that this genetic change is changing the genetic code in some sort of way that is causing the gene not to function properly within the retinal cells.”
With a few exceptions, she said, a general eye exam will not reveal the underlying genetic explanation for retinal disease.
“That’s where genetic testing is necessary to rule in or identify which one of these 200-plus genes could be the underlying explanation and thus, more definitively rule in an inherited condition and provide a more definitive specific genetic diagnosis.”
The most common pattern for inherited retinal diseases to occur is a recessively inherited condition, the result of inheriting a genetic variation in two copies of the gene, one of those copies inherited from mom and one from dad.
“In these recessive conditions, generally, there may be no family history of anybody else in the family with similar conditions, and that’s because individuals can be carriers, and they may carry one copy of a variation and one copy of their gene, but they have another that can compensate.
“Carriers can be asymptomatic and run through multiple generations and not even know that they’re carriers, and it isn’t until two carriers meet that there’s even a chance for both of them to pass on the genetic change.”
Specific Genetic Identification Versus No Clear Explanation
Counselors help in multiple ways as a family or patient is working toward a genetic diagnosis. Place can begin counseling families before testing, gleaning family history details, reviewing complexities of different inheritance patterns, and looking into what can and cannot be learned from testing.
“It’s also exploring with patients and families whether this is the right time for genetic testing. Is this something that the individual is ready to move forward with or is it something that maybe should be discussed or pursued a later time?”
Counselors can work with families after testing, reviewing the result, whether it be that the testing identified a specific gene or that no clear explanation was found, which happens 30 percent of the time, Place said.
No clear explanation could mean a negative result or an inconclusive result. A negative result can mean no genetic variations were identified. An inconclusive one could be that variants were identified within one to two genes, and the lab does not currently have enough data to classify those variants as disease-causing, but they also cannot be ruled out as not disease causing, she said.
“Sometimes additional testing of other family members may be helpful in resolving the significance of those variants, or that it’s going to take some time and more genetic knowledge is needed to better classify those variants.”
Working with a counselor also helps sort out next steps to take, including the possibility of periodically checking back with your genetic counselor to see if more recent research has updated results or new testing options.
“A True Privilege” To Create Relationships
Long-term relationships can develop between counselors and families after testing. If the test identified a specific gene, they discuss the result, assess the risk of other family members having the mutation, coordinate whether they should get tested, and maintain communications going forward about potential genetic-related treatments and therapies.
Place said it may not be the case with every counselor, but long-term relationships with families are the norm in her work.
“I think every clinic and counselor’s experience will be a bit different. I have the true pleasure of working within an IRD clinic where we’ve had long-term relations with the families, and I get to see families back over the course of their visits with us, and so it is a true privilege to be able to create these longer relationships with families.”
Her approach to testing is that a patient diagnosed with any type of IRD should undergo a full IRD panel testing so as not to miss a particular gene.
She also said it’s important for the patients and families to have back-and-forth relationships with their ophthalmologists.
“It’s definitely a two-way relationship, continuing to stay engaged with your providers, but your provider also thinking about being on top of the different testing options that are available.”
Getting Genetically Tested
A person needs a doctor’s order to be genetically tested. Diagnostic testing is done on a patient’s blood or saliva sample at a clinically certified lab that analyzes a specific set of genes identified to be the cause of retinal condition.
ACMG is a place to locate a Medical Geneticist (MD/physician), as well as medical genetics clinics. The search ‘Find a Genetic Service’ can be used to locate a genetic professional.
Search engines in both organizations bring up regional options by entering your zip code. Counselors can meet in-person with patients or, depending on the clinic, via telehealth, by phone, video conferencing, and other virtual methods.
Testing resources also can be found through medical or clinical genetics’ departments in your hospital system.
Also, Sofia Sees Hope has donated more than $140,000 to fund free genetic testing for individuals with inherited retinal disease through the My Retina Tracker® program, launched and managed by the Foundation Fighting Blindness. The program is an open access, no-cost genetic testing program for individuals with a clinical diagnosis of an IRD.
“So much has changed in terms of access to genetic testing for inherited retinal diseases over the last several years, and it’s more available to patients than it ever has been in the past. I would say this is really a good time to work toward getting a genetic diagnosis – getting genetic testing if you haven’t had it or re-engaging with your providers if you’ve had testing years ago without a positive result and discuss updated testing options.
“There are resources out there and available, so there are plenty of individuals like me that are available to help facilitate testing or get you in touch with the right counselor or medical geneticist to help facilitate testing for you.”
Promising gene therapy research – characterized as having a good potential to restore vision – is underway to help visual impairment caused by a form of Leber congenital amaurosis (LCA) attributable to a mutation in the IQCB1 gene.
Amy Laster, PhD, Vice President of Science and Awards Programs for the Foundation Fighting Blindness, shared the research news as part of a recent LCA Research Update webinar summarizing results of an IQCB1/NPHP5-associated retinal disease Scientific Advancement Workshop conducted a week earlier.
Laura Manfre, Sofia Sees Hope Co-Founder and President, said more than 40 leading experts in ophthalmology and gene research gathered for the virtual workshop to share research and patient perspectives and identify the next steps to advance treatment for the patient community. Hope in Focus ( formally Sofia Sees Hope) and the Foundation Fighting Blindness hosted these Scientific Advancement Workshop to widen the circle of research awareness, build a framework or platform for sharing knowledge, foster collaboration among stakeholders, identify gaps, and set priorities for action. The format was based on a similar program run earlier for the RDH12 gene.
“Our objective today is to engage you and our IQCB1/NPHP5 community to seek to advance treatment for ourselves and our loved ones…” Manfre said in her introduction.
“There are no easy answers and there are no quick or fast solutions; just wanted to set that expectation up front even as we are very excited to share the news that we have for you.”
Early-stage translational research
The reported results are from early-stage translational research, which involves moving discoveries from basic science and animal models to applying them in human clinical trials.
The news comes after a successful proof of concept or feasibility study by Dr. Gustavo D. Aguirre, VMD, PhD. He is Professor of Medical Genetics and Ophthalmology at the School of Veterinary Medicine, University of Pennsylvania, and he identifies dogs with inherited eye and retinal degeneration.
Dr. Aguirre will be presenting results of his proof of concept gene therapy study on LCA-NPHP5 dogs in a paper soon to be published in a peer-reviewed journal. The research is detailed in bioRxiv (pronounced bio-archive), a repository for preprinting papers prior to publication.
Laster said the study showed that photoreceptors in treated areas had structural improvements and the dogs had improved visual function.
Researchers sent dogs through an obstacle course under dim light and under bright light. Navigating with their treated eye, the dogs had faster travel times and fewer collisions than when they navigated using their untreated eye.
She called the findings very promising, saying, “We’re excited about these results.”
Laster also cited ongoing clinical studies suggesting that the structure of the central retina or macula is preserved for many years despite having significant loss of vision.
“This, if you will, dissociation between the structure and function suggests that a gene therapy targeted at the central retina not only could work but has a good potential to restore lost vision,” she said. “So we build on this proof of concept and clinical knowledge toward translating these laboratory-based research concepts into clinical trials for patients.”
Next steps
The next steps include designing clinical trials and identifying relevant endpoints and outcomes to measure the safety and effectiveness of the gene therapy.
Webinar speaker Todd Durham, PhD, Vice President of Clinical and Outcomes Research at the Foundation, said the dog model studies began about four years ago. He said it is unknown when clinical trials would begin because more work needs to be done prior to launching them. Durham emphasized the importance of the research results, saying, “They’ve very much ticked off a major milestone in this proof of concept canine model.”
Scientific workshop participants also learned that Dr. Aguirre and his colleague, Dr. William A. Beltran, DVM, PhD, co-founded a Philadelphia-based biotechnology company called LuxFiat Therapeutics.
Laster said this would position the scientists to advance the gene therapy into clinical trials and said that the Foundation will continue to do all that it can to accelerate any clinical development.
The Foundation, the largest private funder of research for treatments and cures of blinding retinal diseases, has raised nearly $800 million since its inception and currently funds more than 80 research projects globally. Dr. Laster oversees the Foundation’s preclinical research portfolio consisting of research awards in funding programs that support career development, laboratory-based science research, translational research, and multi-investigator program projects.
In the question-and-answer session, Durham discussed a query from the audience as to whether it was unusual to receive an incorrect diagnosis of retinitis pigmentosa (RP) before later getting a confirmed genetic diagnosis of Leber congenital amaurosis from Spark Therapeutics.
Durham said it was not unusual and that it was great the audience member got a genetic diagnosis.
“The clinical manifestations of what many ophthalmologists observe when they do an exam can overlap quite a bit from various conditions,” he said. “Ultimately, at the end of the day, the fact that you got a genetic diagnosis is most informative for you, and that’s our hope that there will be more access to genetic testing. Just to reassure you, I don’t think your story is very unusual at all, unfortunately, but hopefully access to genetic testing going forward is going to make that a less frequent story.”
Supporting the Leber congenital amaurosis community
Manfre, responding to a question about help specifically for those with the IQCB1/NPHP5 mutation, said Sofia Sees Hope supports the entire Leber congenital amaurosis community and suggested looking at the website’s Resources page and joining a highly active IQCB1/NPHP5 Facebook group that she joined because her daughter Sofia has the same genetic variant.
Durham also devoted the beginning of the webinar delivering preliminary information from an ongoing patient survey on perspectives of people affected by LCA or RP and their caregivers.
He said the survey results will be available to the community after final analysis of the data.
Here are the topics addressed in the survey developed by Sofia Sees Hope and the Foundation:
Diagnostic Journey
Current Best Corrected Visual Acuity
Visual Symptoms
Other Related Conditions
Worries
Impact on Your Family Overall
Participating in Clinical Trials
Motivations for Participating in a Clinical Trial
Anything Else to Share with Researchers.
Under the last topic, a participant responded: “Time is vision. Please hurry for IQCB1. Give us hope.”
As the Supervisory Physician in the FDA’s Division of Ophthalmology, Dr. Chambers discussed vaccines and processes necessary for drugs to be approved for human use in our February 16 webinar episode: “Let’s Chat About…What it takes to receive approval for a new treatment for rare disease.” Sofia Sees Hope Director of Marketing and Communications Elissa Bass moderates the free monthly webinar series. You can watch the webinar here.
Dr. Chambers joined the FDA in 1987 as a primary reviewer for ophthalmic drug products and in 1990 became a Supervisory Medical Officer for Ophthalmologic Drug Products. He has supervisory responsibility for the clinical review of ophthalmologic drug products and ophthalmic therapeutic biologic products submitted to the Center for Drug Evaluation and Research. He has clinically reviewed more than 100 ophthalmology drugs that have received FDA approval, including the first gene therapy, LUXTURNA®, approved in December 2017. The drug – administered through subretinal injection – is a human-engineered virus containing a healthy version of the RPE65 gene that causes blindness in patients with a form of Leber congenital amaurosis (LCA) called LCA2 (RPE65).
Vaccines: “We’ve Got That Down”
Talking about the recently authorized COVID-19 vaccines, Dr. Chambers said it wasn’t a matter of starting from scratch. “We know how to make vaccines. We’ve been making vaccines for over a hundred years. We make new vaccines every year. The flu shots that come out are a change in the vaccine every year and we put a vaccine out every year that’s specific to different strains of the flu. Every year. So, we’ve got that down.”
The process did differ in two aspects because of the urgency to quell the pandemic.
“What happened with COVID is the federal government said, ‘You companies go make the vaccines. We’re still going to go through the normal process of testing it, having the FDA go and review it, but don’t wait to see if the product works or not before you make up all those doses. Make them now. And we’re going to pay you for them whether it works or not.’
“So, the companies went and did that. We didn’t skip any steps. We know how to make vaccines. We did what we typically know. We made a series of vaccines and at the same time the companies were mass-producing, as everybody would suggest now, not enough, but made a number of doses out so that when the products got approved, they already had doses made. They didn’t have to start manufacturing doses.”
The second distinction is COVID-19 – which has killed more than 550,000 Americans and more than 2.6 million people worldwide – created a public health emergency requiring urgent mitigation.
Rather than getting FDA approval or clearance, COVID-19 vaccines received Emergency Use Authorization (EUA), one of several tools the FDA is using to help make certain medical products available quickly during the pandemic. Under an EUA, the FDA makes a product available to the public based on the best available evidence, without waiting for all the evidence that would be needed for FDA approval or clearance.
EUAs are effective until the emergency declaration ends, and they also can be revised or revoked by the FDA as it continues evaluating available data and patient needs during the public health emergency.
Developing gene therapies to improve vision also meets fast-tracking requirements because vision loss is considered serious. Fast-tracking gene therapy in ophthalmology means extra meetings and FDA communication. “But you’re not skipping any steps at all,” Dr. Chambers said.
Improving Visual Acuity
The FDA is a gatekeeper requiring that a product be safe and efficacious for its intended population before it can be marketed for human use. Dr. Chambers regularly talks with patients and solicits comments from groups about what is important to them in the search for potential treatments or cures. The information then can be modified into endpoints, or outcomes, measured scientifically through clinical trials.
“We strive to approve products that are going to benefit patients. That’s who’s going to take them. That’s who they’re for, that’s what we’re trying to go and match.”
Dr. Chambers said his personal preference is cures.
“I like diseases to go away. My endpoint, if given the choice, would be to have something go away. But I’ve got to have a product that’s capable of doing that too, so there’s a reality that sets in that I may not get a product that cures, that does everything I would like it to go and do, but we strive for as many of those things as possible and to then try to include them in the trials.”
As an example, he cited visual acuity (clarity of vision) and the ability to drive.
“For better or worse, in the United States, if you want to be independently mobile, as far as living alone in many parts of the country, you have to be able to drive…and every state in the United States has a visual acuity value that if you’re not at the visual acuity or better, you can’t get a driver’s license…
“We think visual acuity is an important thing to be able to improve for patients. Not because they say they want it but because we know if they don’t achieve that level, they’re not going to be able to drive and they’re not going to have the mobility that we know people want.”
Whether someone can see better in some aspect is an important endpoint, even if it means vision is not completely restored. “I frequently make the comment that my head is going to hurt just as much if I get hit by a ball that I saw or that I didn’t see. If I have a blind spot and I can now not see a ball coming to me and I get hit with that ball, it’s going to hurt. It would have been nice if I had had the full field of vision so that I could see the ball coming and avoid it. So, if I improve my field of vision, even if it’s not dead center, even if it’s not visual acuity, it’s still a benefit to me.
“You’ll see us potentially approve products on things less than fixing the whole thing, but fixing some portion, and again, we’re absolutely open to suggestions by people of things that they think benefit them that we could use as endpoints.”
Research Models
Mice and rats, cats and dogs, rabbits and monkeys – they all play important roles in developing new treatments and drugs. With inherited retinal disease, dogs take the cake.
Researchers use animal models that most resemble humans, and in the case of LCA, studies showed dogs gained improved vision, leading to the federal approval of the groundbreaking drug LUXTURNA®.
Lancelot, a Briard descended from an ancient breed of large herding dogs in France, carried the same RPE65 gene that caused his blindness.
By contrast, rats would not make for good study models in retinal research because they do not have a macula. “Rats are more interested in going around in the dark. Their eyes are different,” Dr. Chamber said. “You want to pick an animal that has similar receptors in that species.”
Lancelot and his cousins paved the way for FDA approval of the first-ever gene therapy for inherited disease in humans.
Road to Approval through Clinical Trials
The goal of the FDA is to approve a product proven to be safe and efficacious. The product’s potential adverse events are weighed against its benefits in the balancing act of risk versus reward.
The agency regulates interstate commerce, acting as a gatekeeper for any product intended for human use. Because a biotechnology company probably wants to ship the investigational drug to clinical investigators in many states, it first must seek an exemption from that legal requirement. The exemption is granted after the company submits its research for review. “If we say nothing, they’re allowed to proceed. If we have an objection, we tell them in 30 days.”
Beware of phony trials, Dr. Chambers said. The website clinicaltrials.gov lists both trials that have been issued an IND number and those overseen by the FDA. It also lists trials not reviewed by the FDA.
“First thing: Ask what the IND number is,” he advised. Dr. Chambers noted that clinical trials, for better or for worse, are never conducted for the people in the trial. They are geared to inform what is going to happen in the future with the product. Rare diseases – such as the more than 25 forms of LCA and other rare inherited retinal diseases (IRDs) – present bigger challenges in finding participants for clinical trials because the rare disease community inherently represents fewer people. The definition of a rare disease in the United States is one affecting fewer than 200,000 Americans.
If only 30 people are studied, you are likely to see adverse events that occur in 10 percent or more of individuals, he said. If you study 300, adverse events can be picked up at a rate of 1 percent or above.
“It’s all about the numbers, numbers, numbers, numbers…It’s a numbers game.”
The process wends its way through more protocols, comparisons, studies, and trials until a company submits a marketing application reviewed by experts at the agency.
The FDA may hold Advisory Committee meetings for public comment from external reviewers, special government employees, patients, consumers, and advocates. In the case of LUXTURNA®, Sofia Sees Hope Co-Founder and Board Chair Laura Manfre testified at an Advisory Committee meeting on behalf of Spark Therapeutic’s application.
FDA oversight does not end after it approves a drug and a biotechnology company begins marketing it for human use.
“We now start monitoring for adverse events that might occur with the product,” Dr. Chambers said.
The process of receiving federal approval of products for human use can be long and expensive: LUXTURNA® research, development, and approval took 12 years and $500 million. The rewards, though, can be priceless, in helping children and adults see the world in a new light.
Had he received a more definitive rare disease diagnosis in 2003, Alan Gunzburg said he might not have lost so much vision and still might be able to drive.
In 2016 – 13 years after his initial diagnosis – the Greenwich, Conn., man learned his vision and hearing loss was caused by Adult Refsum Disease (ARD), a genetic metabolic disorder with symptoms that perhaps he could have staved off years ago through dietary restrictions.
Doctors initially diagnosed Gunzburg with retinitis pigmentosa (RP) – a rare inherited retinal disease (IRD) causing progressive loss of peripheral and night vision. Those are also symptoms of Refsum disease, which, if undiagnosed, can be life-threatening.
The disorder results in a buildup in the nerves and liver of phytanic acid, a type of fat found in certain foods. Other symptoms are loss of smell and hearing, numbness, unsteadiness, itchy skin, and shortened fingers and toes.
His story reflects the plight of many people living with a rare disease because the more than 7,000 rare diseases in the United States are just that – rare.
It’s difficult to correctly diagnose rare diseases when little information exists about them.
Some families living with rare disease find they must create their own advocacy avenues to educate the public and the medical community about diseases they’ve never heard of.
Gunzburg created the Global DARE Foundation with the mission of Defeating Adult Refsum Everywhere. His website gets the word out about the disease and gives information on symptoms, treatments, and research.
Laura Manfre, co-founder and board president of Hope in Focus (formally Sofia Sees Hope), took that same route in 2014 after doctors genetically diagnosed her daughter with a form of Leber congenital amaurosis (LCA). As a global patient advocacy organization, Sofia Sees Hope helps transform the lives of those affected by blindness caused by LCA and IRDs by generating awareness, supporting affected families, and raising funds to advance research for diagnosis, treatments, and cures.
Creating Rare Disease Advisory Councils
The global phenomenon of Rare Disease Day exists to create awareness of rare disease, characterized in the United States as affecting fewer than 200,000 people. With more than 7,000 rare diseases, 25 million to 30 million Americans are affected by rare disease. That means one in 10 Americans suffer from rare diseases, and more than half of them are children. The European Organization for Rare Disorders (EURODIS) organizes the international campaign.
Nationally, Rare Disease Day brings together each state’s RAN ambassador – in Connecticut’s case, Volunteer State Ambassador Lesley Bennett – along with patients, caregivers, doctors, advocates, legislators, academics, and business and biotech leaders to generate awareness, increase patient and caregiver support, and drive research for treatment and cures.
This year’s event focused on creating Rare Disease Advisory Councils (RDACs) in all 50 states through NORD’s Project RDAC. Councils are made up of various stakeholders, including patients, caregivers, doctors, insurers, biotechnology companies, researchers, and state officials.
Project RDAC’s goals are to optimize existing councils and increase the number of groups nationally by opening collaborative opportunities among councils, creating educational resources to guide them, and helping more states pass legislation that establishes high-functioning councils.
More than a dozen states have RDACs, 12 are pursuing RDAC legislation, and another 23 states do not have an RDAC.
Connecticut is working toward creating a permanent RDAC task force, after a temporary group disbanded in 2019. Check out this map to see if your state has an RDAC or if NORD is working on legislation to create one. To start an effort in a state, click here.
Telling Rare Disease Stories
NORD’s Kristen Angell moderated the virtual celebration that featured more than two dozen people, sharing stories about the struggles and successes in the world of rare disease. A recording of the celebration will be available soon.
Suzanne Candela literally told an uplifting story as outreach and mission coordinator for Patient Airlift Services (PALS) with the motto: “Going Above and Beyond to Lift People Up.”
Volunteer pilots help eliminate logistical barriers to treatments by using their own aircraft, fuel, and time to fly patients to appointments. Over the course of 10 years, the company helped 2,900 families in 23,000 flights, covering more than 5.4 million miles. Candela told of a girl flown from northern Maine to Boston for repeated cancer treatments. The patient has flown on PALS flights about 60 times and counting.
The service could eliminate transportation barriers for participants in out-of-state clinical trials. The company also has flown 900 flights bringing combat-wounded veterans to appointments.
Connecticut State Sen. Cathy Osten described the story behind proposed legislation that she and State Rep. Christine Conley introduced this session to help a local family struggling to pay for special food for their two children diagnosed with phenylketonuria (PKU). The family’s share of the cost is about $36,000 per child per year. Osten said insurance companies hesitate to pay but the expense is well worth it when it comes to the quality of life for people with PKU.
David Leeds of Avon has the rare disease Hereditary Angioedema with normal C1 Inhibitor (HAE-nC1Inh), a new form of hereditary angioedema (recurring episodes of swelling) identified in 2000.
If he goes to the hospital in this time of the COVID pandemic and no one knows about his rare condition and no one can speak on his behalf, Leeds said, “We just have to hope that my rare disease doesn’t kill me before they send me home.
“I have to know everything about my disease because my doctors don’t.”
John Hopper, one of the emcees of the virtual celebration, heads the Greenwich-based Fibrolamellar Cancer Foundation that advocates for people living with fibrolamellar carcinoma, a rare liver cancer that usually occurs in adolescents and young adults with no history of liver disease.
Hopper, who also co-chairs NORD’s Rare Cancer Coalition, said his strategy is to be what he calls “the mouse that roared.”
“That means we know we’re small, but we know we have to be loud,” Hopper explains on his foundation’s website. “Most people don’t know about rare diseases. Unfortunately, a lot of people don’t care about them. Our strategy is to be that loud voice – that leader – to make sure that every stakeholder from government to academia to pharmaceutical pays attention to this cancer and understands that working on this small cancer may lead to bigger things too for the rest of them.”
Hopper encouraged all the participants in the virtual rare disease day event to be that mouse that roars.
Fifteen states have established a Rare Disease Advisory Council (RDAC) to give the rare disease community, including those living with Leber congenital amaurosis (LCA), a stronger voice in state government. Another dozen states are actively working to establish RDACs this year.
With assistance from the National Organization for Rare Disorders (NORD), patient organizations, such as Hope in Focus (formally Sofia Sees Hope), and the broader rare disease community, RDACs around the country work to help states strategically address barriers faced by people living with rare diseases. The councils give stakeholders an opportunity to make formal recommendations to state leaders on critical rare disease issues, including increased awareness, diagnostic tools, and access to affordable treatments and cures.
Sofia Sees Hope, based in Ledyard, Conn., annually gives information to legislators on the Connecticut General Assembly’sPublic Health Committee, letting them know that rare disease advocates and those living with a rare disease, need state and federal support in crafting legislation to help the rare disease community.
The last day of February each year is officially Rare Disease Day, a time to raise awareness among the public and decision makers about rare diseases and their impacts on patients’ lives. NORD sponsors Rare Disease Day in the United States, alongside its sister organization, the European Organization for Rare Disorders (EURODIS), which organizes the official international campaign.
A disease is defined as rare in the United States if it affects fewer than 200,000 Americans. LCA and other inherited retinal diseases (IRDs) are among the approximately 7,000 rare diseases that exist nationally, affecting 1 in 10 people. These diseases include more than 500 types of rare cancers and all pediatric cancers.
Between 25-30 million Americans live with a rare disease, including about 300,000 in Connecticut.
NORD’s Connecticut Rare Action Network, along with other such groups nationwide, will highlight RDACs as part of its virtual celebration of Rare Disease Day 2021. Connecticut’s Rare Disease Day celebration will be at 9 a.m. ET, Friday, Feb. 26. You can register to participate in this free event by clicking here.
NORD also just released its sixth edition of its State Report Card* that analyzes the 50 states and Washington, D.C., on eight policy issues that impact the rare disease community. The organization launched its report card project to evaluate the effectiveness of states serving people with rare diseases.
Each state has its own report card that addresses Medicaid Financial Eligibility, Medicaid Nutrition, Newborn Screening, Prescription Drug Out-of-Pocket Costs, Protecting Patients in State Medicaid Programs, Protecting Patients in State-Regulated Insurance, Rare Disease Advisory Councils, and Step Therapy (trying less expensive options before “stepping up” to drugs that cost more).
RDACs advocate for patients and caregivers
State governments make decisions every day affecting the rare community. They play critical roles in ensuring access to health care providers, services, and treatments needed to thrive, along with the design of their Medicaid program benefits, and regulation of some insurance plans. The councils offer forums for discussion about these issues.
As one Connecticut legislator said at a previous celebration, having one day to recognize rare diseases is not enough.
“It needs to be Rare Disease Day every day in the state of Connecticut,” said State Rep. Jonathan Steinberg, co-chairman of the General Assembly’s Public Health Committee.
Connecticut Volunteer State Ambassador Lesley Bennet – along with ambassadors nationwide, doctors, researchers, advocates, caregivers, patients, legislators, and business leaders – take this time to advocate state-by-state for better resources and outcomes for people living with rare diseases.
Bennett said many of their patients have difficulty getting access to services because people don’t understand the disorders.
Patients, caregivers, families, and providers in North Carolina created the first RDAC six years ago; 15 states have active councils with1 2 more on their way toward fruition, for a total of 27 states.
Another 23 states, including Connecticut, do not have such councils but efforts continue through NORD’s Project RDAC, launched last fall. Connecticut established a task force to study whether to create an RDAC, but the group disbanded in 2019.
Check out this map to see if your state has an RDAC or if NORD is working on legislation to create one. To start an effort in a new state, go to RDAC@rarediseases.org.
Council composition varies from state to state in size, duties, and accountability requirements. It also depends on the type of entity that houses the RDAC, such as a state department of health or a non-profit organization.
A council typically comprises various stakeholders, including patients, caregivers, doctors, insurers, biotechnology companies, researchers, and state officials.
Project RDAC aims to optimize the existing councils and increase the number of groups nationwide by opening collaborative opportunities among the councils, creating educational resources to guide them, and helping more states pass legislation establishing high-functioning councils.
