The event runs from 8:30 a.m. to 3 p.m. at The Goodwin Hotel, One Haynes St., Hartford, CT. It is hosted at no cost to participants; breakfast and lunch will be provided.
The workshop features an opportunity to speak directly with members of Congress from Connecticut about the Orphan Drug Act (ODA) of 1983. Orphan drugs are medications intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States, or that affect more than 200,000 people but are not expected to recover the costs of development and marketing a treatment drug, according to the Food and Drug Administration.
Online registration closes at noon, Tuesday, April 30.
Register Here
The ODA encouraged increased development of drugs for rare diseases. More than 450 orphan therapies have been developed by private industry since its enactment, compared with 10 therapies, 10 years before the 1983 legislation. Thirty years later, in 2013, orphan therapies comprised one-third of all drugs approved by the FDA, according to NORD.
NORD founders helped spearhead the Orphan Drug Tax Credit, characterized as one of the most important incentives for orphan drug development, and enacted as part of the ODA. The provision allows a 25 percent tax credit for sponsors on certain research and development costs for orphan drugs. NORD said that coupled with other incentives in the ODA, the tax credit has proven its efficacy, and it is in danger of repeal.
For information on RAN events nationally, check your state RAN and sign up to receive notice of upcoming activities.
Upcoming NORD/RAN events include:
A workshop in Massachusetts, like that of Connecticut’s: NORD Massachusetts Rare Action Network Patient Advocacy & Orphan Drug Workshop; Friday, July 19, from 8:30 a.m. to 3:00 p.m.
“Look like you can see!” Dante Priebe implores to his panicked, visually impaired sister Sofia as she struggles behind the wheel to make a three-point turn in her driveway.
“I do this horrible, 18-point turn and a cop car drives by in those three minutes,” Sofia says.
She ends up in the street and Dante yells at her to pull into the neighbor’s driveway and “act like she can see.”
The car ends up on their lawn, with Sofia shouting at her brother, “I don’t want to do this anymore!!!”
The audience laughed, and so did Sofia, as she recounted her story during a discussion at “A Rare Opportunity,” a gathering of more than 100 people to hear stories from people with Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs).
Sofia is the daughter of Laura Manfre and Chuck Priebe, co-founders of Hope in Focus (formally Sofia Sees Hope), dedicated to helping people affected by LCA and other IRDs. Sofia’s parents founded the organization after her 2013 genetic diagnosis, giving hope that genetic research could produce sight-saving treatment.
Nicole, of Brooklyn, NY, joined a panel discussion with Sofia, Christian Guardino and Diana Owen for an exchange about what it’s like to live with visual impairment.
In the panel moderated by Nicole’s friend, author and professor Dr. Amy Bass, the participants said they wished people would be more aware of others with disabilities.
Nineteen-year-old Christian of Patchogue, NY, said he wishes he could take part in a common teenage rite of passage.
“I think one of the biggest things is I see all of my friends driving and getting their licenses, and it makes me want to do it even more.
“But I feel like I’m saving a lot of money.”
In 2017, Christian stepped onto the America’s Got Talent audition stage and blew away the judges with his rendition of the Jackson 5’s “Who’s Lovin’ You.”
He recently released his first original song, “Waiting,” executive produced by country singing star Hunter Hayes.
Christian lived with degenerative vision due to LCA2, known as LCA-RPE65, since he was a toddler, but all that changed when he underwent experimental surgery five years ago in a clinical trial for a revolutionary genetic treatment. His vision improved dramatically with the treatment called LUXTURNA™. Spark Therapeutics developed the drug that the Food and Drug Administration approved at the end of 2017.
Independence vs. asking for help
Diana Owen, Head of School at Pine Point School in Stonington, CT, was diagnosed in her 40s with a macular hole, a condition resulting in vision changes over time.
She lives with a constant, sometimes frustrating, sense of having to work around situations to accommodate her vision.
“When my issue developed what I didn’t understand was about acuity,” she said.
Her visual acuity manifested as darkened spots, haze and distortion.
A macular hole is a small break in the macula, in the center of the eye’s light-sensitive tissue called the retina. The macula provides the sharp, central vision needed for reading, driving and seeing fine detail. It can cause blurred and distorted central vision.
Nicole said she never wanted to use a cane: “When you open the cane, this is the cane and I’ve disappeared.”
Sofia is a high school sophomore who savors independence. She has LCA with a mutation of her IQCB1/NPHP5 gene, one of the more than 25 gene mutations known to cause the disease.
“I’m very stubborn,” she said. “I’d like to do things on my own. Being blind doesn’t mean full no-vision. (People) try to help me with things and, I’m like, I got it!”
And she does! In academics, dancing and rowing. Sofia’s a spokesperson for “Remote Coxswain” technology, invented by her rowing coach, so she can row solo. The tool features a remote-controlled rudder than can be operated by a coxswain up to 500 feet away.
Transitioning to dinner, the panel and the audience heard Christian’s new song fill the grand room. Listen for yourself.
On a romantic getaway, as her boyfriend gazed at the starlit sky, she gazed at the vast darkness. Same with the twinkling lights at the tip of New York’s Staten Island.
“I was 19 years old when I discovered I couldn’t see stars.”
That’s when the actress and future author received her diagnosis of Retinitis Pigmentosa (RP), a rare, debilitating retinal disease. Her photo receptors were dying; no treatment, no cure.
Hearing she’d lose her vision by age 30 came as “absolute blindsiding news.”
Kear shared her story with more than 100 people gathered at Lake of Isles in North Stonington, CT, on March 30. Sofia Sees Hope Co-Founder Laura Manfre characterized the event – which also included a panel discussion – as “a chance to hear from incredible people who have faced head-on an almost unimaginable challenge and chosen hope over defeat.”
Kear felt incredulous at her diagnosis.
She’d always chalked up any stumbles in life to being accident prone, or “I thought I was some airhead who didn’t pay attention.”
She had plans: She was going to be a star of the stage, fall in love, get married, have children.
“Nowhere in these plans was room for losing my vision by 30.”
A River Called Denial
Upon her diagnosis, Kear did what a lot of people might not have expected: “I decided not to think about it.”
Plus, she thought, by the time she turned 30, “I would be ancient by then.”
She learned to drive, kind of. Kear didn’t need a car in New York, but when she temporarily moved to Los Angeles for acting, only three days passed before she realized she’d made a colossal mistake. She drove anyway, with her idiosyncratic driving posture, prompting her sister to tell her maybe she should lean back a little, an exchange recounted in her book:
“What are you talking about?” I snapped, concentrating on my left turn.
“You don’t notice how close your face is to the windshield?”
It was true. My nose was almost touching the glass, my chest nearly pressing the wheel …
“There’s no law about sitting too close to the windshield,” I shot back. “Just sit back and enjoy the ride.”
I couldn’t see my sister’s face, but I bet she looked like she was enjoying the ride about as much as a turn on the Tilt-A-Whirl with a stomach full of corn dogs …
My uncool driving notwithstanding, I did a decent job of getting from point A to point B without dying or killing anyone. In general.
Kear fared better in restaurants than on the road. She learned to order the Caesar salad because it’s usually on the menu she couldn’t see, and she’d ditto her dining partner’s choice for the main course.
She traveled to Paris and London. She enrolled in the San Francisco School of Circus Arts where she learned to be a contortionist and earned a red nose.
“Following every rainbow, climbing every mountain,” Kear told her audience, until she finally gave up the ruse.
‘Anything Is Possible’
“I had realized that my vision had an expiration date … I could carpe diem as much as I wanted, but I had to reckon with my vision loss.”
At 33, after falling in love, marrying and having two of her three children, she faced her diagnosis and reached out to New York’s services for the blind.
The gravity of support and resources empowered her, connecting her to visually impaired people around the world.
“I know now that anything is possible.”
Kear ended her presentation by reading one of the tips that accompany each chapter of her book.
Tip #18: On glass doors. Walk into a glass door once, shame on the door. Walk into it twice, shame on you. Walk into it three times, get yourself a (*%&#*) game plan.
Sixth-grader Daniela Delgado told Connecticut lawmakers on Rare Disease Day that she lives with rare disease just like 30 million other people in the United States – and just like them – she matters.
“We are not a burden. We are human beings just like everybody else,” Daniela told about 130 people gathered at the Capitol in Hartford for Rare Disease Day. The day is celebrated nationally and globally on the last day of February each year. (Click here for state-by-state information.)
Daniela was diagnosed with not one, but two, rare diseases: von Willebrand Disease, a rare, lifelong bleeding disorder; and Ehlers Danlos Syndrome, a group of disorders affecting connective tissue supporting the skin, bones, blood vessels and many other organs and tissues.
She needs expensive drugs to treat her disease and ease her symptoms; without them, the cost would be exponentially more for hospitalizations.
“These are real treatments, and they keep us alive,” she said. “We need this medication to live.”
Daniela is a patient advocate from Sandy Hook, CT, who at age 4, with the help of her parents, created Daniela’s Little Wish, bringing joy to kids facing serious illnesses by baking and delivering one-of-a-kind birthday cakes.
She joined about two dozen speakers at a legislative informational session that included legislators, patients, doctors, researchers, nurses, caregivers, advocates, business people and a representative of Sofia Sees Hope.
7,000 Rare Diseases in the US
Rare disease is more common than most people realize.
A rare disease is defined as any disease, disorder, illness or condition affecting fewer than 200,000 people in the United States. An estimated 25-30 million Americans, almost 1 in 10, have rare diseases. In Connecticut, an estimated 300,000 people have rare diseases.
Connecticut may be the Insurance Capital of the World, but the Nutmeg State gets an F when it comes to individual insurance protections, according to Connecticut’s rare disease report card prepared by the National Organization for Rare Disorders and NORD’s Rare Action Network (RAN), the hosts of Connecticut’s Rare Disease Day.
The state requires some insurers to offer guaranteed plans to a limited number of people. It does not have an individual mandate and has not enacted a reinsurance waiver to keep insurance affordable for people with pre-existing conditions. Connecticut had minimal limits on issuing short-term, limited-duration health plans or association health plans.
Father Nikolas Karloutsos
State Rep. Joe Aresimowicz, Democratic House Speaker, and State Sen. Len Fasano, Republican Senate Minority Leader, have introduced several pieces of legislation addressing medical education in screening for rare cancers and assistance for patients and families with developmental disabilities. Fasano also helped the state become one of the first to add Adrenoleukodystrophy (ALD) to Connecticut’s Newborn Screening (NBS) panel.
Aresimowicz said the focus of the event was not on politics or political parties.
“We are here because we want to make Connecticut a better place.”
Fasano told the gathering: “This is a civil rights issue to get the proper medications and research to go forward.”
Greta Stifel, who has two rare diseases on top of cancer, detailed her grueling journey of misdiagnoses and many surgeries. In 2016, she established the Stifle Cancer Foundation to bring awareness to a type of cancer comprised of Neuroendocrine Tumors (NETS).
“We are the ‘Rare Rebels’,” she said. “We are the ‘Rare Revolution’.”
She is a constituent of Aresimowicz, and the proposal behind the pending legislation of House Bill 6522 comes from her. The bill’s title is: An act concerning continuing medical education in screening for inflammatory breast cancer and gastrointestinal cancers.
Stifle said the legislation is a step in the right direction, but the state needs to do much more with rare disease awareness, education, funding and research. “
Connecticut actually should be the Silicon Valley of Rare Disease,” she said.
State Rep. Jonathan Steinberg, chairman of the General Assembly’s Public Health Committee, said having one day to recognize rare diseases is not enough.
“It needs to be Rare Disease Day every day in the state of Connecticut.”
Steinberg, along with RAN’s Volunteer State Ambassador Lesley Bennett, said the legislature needs to form a Rare Disease Advisory Council to find treatments, fund research and advocate for Connecticut’s constituency living with rare disease.
“A lot of our patients have problems getting access to services because people don’t understand the disorders,” Bennett said.
The advisory council would be comprised of patients, patient advocates, doctors, researchers, business leaders and community members to address the emerging public health priority of rare diseases, including LCA and other IRDs.
Erica Mumm, a Clinical Assistant Professor at the Quinnipiac School of Nursing and mother of a son with a rare genetic disorder, said the system needs to change. She also supports the creation of a rare disease advisory council.
Not a one-size-fits-all community
“We are rare, so we don’t fit into a one-size-fits-all system,” Mumm said.
Her son, who turns 3 this month, has a rare genetic disorder called KCNQ2 encephalopathy, a type of epilepsy that becomes apparent in the first three months of life and is characterized by frequent and difficult-to-treat body seizures.
Mumm advocated for care coordination and described the drain and debilitation she feels as a caregiver. She also advocated for a palliative care network to improve emotional support for caregivers. She has exhausted her savings and said as her voice cracked through tears that her home needs extensive renovations to accommodate her son.
She also implored lawmakers to do away with resetting the clocks twice a year with Daylight Savings Time.
“For us, it’s a change of medication routine,” she said. To keep her son on track with his medications, three weeks before changing the clocks, she must begin making incremental changes in dosages.
A family panel of four caregivers told the group Connecticut needs to support businesses researching and developing treatments for rare diseases.
Alissa Dejonge
“The sky’s the limit because of research,” Alissa DeJonge said. She is Vice President of Research for the Connecticut Economic Resource Center, Inc., and the mother of a 2½-year-old son with severe hemophilia.
Heather Knapp, a panelist and mother of three, described the benefits of the state-mandated NBS program that in 1964 began statewide blood-spot screening for Phenylketonuria (PKU), the same rare disease doctors identified in her son at birth. Early detection and treatments can mean the difference between lifelong impairment and healthy development. Knapp praised NORD for helping her with resources, saying she finally found peace of mind when she connected with the organization.
Panelist Father Nikolas Karloutsos, a Greek Orthodox priest, detailed the difficulties in getting a diagnosis for his daughter, who has a BRAF mutation RASopathy, which probably is Cardiofaciocutaneous (CFC) Syndrome. The very rare disorder particularly affects the heart (cardio-), facial features (facio-) and the skin and hair (cutaneous); it causes moderate to severe delayed development and intellectual disability.
For Jennifer Ianuzzi, it took 20 months until doctors diagnosed her daughter with Smith-Magenis Syndrome, a developmental disorder caused by chromosome 17 microdeletions. She appealed to the group for support for respite from 24/7 caregiving.
Researchers, scientists and professors also presented updates in their fields.
Ching Lau, MD, Ph.D., the Division Head of Connecticut Children’s Medical Center’s (CCMC) Center for Cancer & Blood Disorders and Professor of Genomic Medicine at JAX Laboratory, said that developing and strengthening international genetic research collaborations will help people around the globe access rare disease information through genetic registries. Dr. Lau specializes in finding treatments for children with rare blood, bone and brain cancers.
“We will conquer these diseases at the end,” he said.
Dr. Charles Whitaker, a neuromuscular neurologist at the Hospital for Special Care (HFSC), specializes in adult neuromuscular disorders, such as Amyotrophic Lateral Sclerosis (ALS) and muscular dystrophy. Dr. Whitaker said patients, physicians and experts need to work together to evaluate changes at a policy level that address the special needs of the rare disease population, which, along with having pre-existing conditions, in many instances are highly debilitated. As a clinical researcher working on treatments and cures, he said: “We would love to be part of that cure.”
Gyula Acsadi, MD, Ph.D., said interventions never possible in rare diseases are changing the lives of young children because researchers are focused on discovering genetics and the biology of disease.
“This last five, six years were amazing with how research succeeded,” he said.
Alissa Dejonge’s son listens as she speaks at the podium.
Dr. Acsadi, Division Head of Neurology at CCMC and Professor of Pediatrics and Neurology at UConn School of Medicine, works with children living with Spinal Muscular Atrophy (SMA), the leading cause of death of infants and toddlers of any genetic disorder. SMA robs children of physical strength.
Newly approved NBS for SMA and new treatments administered early in children show remarkable results, he said. Even so, ongoing fights continue with insurance companies unwilling, for example, to pay $15,000 for a treatment that will save $2 million in care. One young patient spent more than 300 days in the hospital before receiving treatment, followed by zero days in the hospital.
“It’s an easy win in terms financially,” Dr. Acsadi said.
Dr. Saquib Lakhani, Clinical Director of Yale Medicine’s Pediatric Genomics Discovery Program, said 30 percent of children in the Intensive Care Unit have rare diseases and very complex needs.
“It’s a collective mistake to ignore rare diseases,” he said. “They have to be addressed.”
Dr. Lakhani specializes in caring for newborns and infants with undiagnosed birth disorders. Using DNA sequencing allows for many more diagnoses, he said.
“It’s been a remarkable change.”
He described a whole exome sequencing test that relies on new technology and allows rapid sequencing of large amounts of DNA with the potential to discover hundreds and hundreds of diseases.
While patients could benefit from this amazing vehicle to find the source of a disorder, they have difficulty getting insurance coverage.
“We don’t know what we’re looking for. (The DNA sequencing) can actually give you the diagnosis that you didn’t have before.”
Moving forward with research and developing treatments for rare disease requires that critical diagnosis.
As Daniela – our young cake-baker extraordinaire living with two rare diseases – summed up in her address to the legislative group:
“We are 30 million and counting. We are alive and we deserve better.”
Members of Connecticut’s General Assembly (CGA) will hear from myriad people and organizations, including Sofia Sees Hope, about patient advocacy and access to treatment during a legislative informational session Thursday in Hartford, in celebration of Rare Disease Day 2019.
This year’s theme is Show Your Stripes, with a call to action for people to literally and figuratively “show their stripes” in support of rare diseases, according to the National Organization for Rare Disorders (NORD), the leading independent nonprofit organization representing the 25 million to 30 million Americans living with rare diseases.
The zebra, the official symbol of rare diseases in the United States, is noted for its black and white stripes that are central to its uniqueness. Everyone has his or her owns stripes, characteristics that make individuals distinct. While each of the more than 7,000 rare diseases are unique, many commonalities unite the rare disease community.
This event is held nationally and in more than 85 countries. It serves as an opportunity to hear from the many voices of those dealing with rare diseases and the daily challenges facing Connecticut patients and their families.
The public is invited to attend the event from 8:30 a.m. to 11 a.m. in the 2nd Floor Atrium of the Legislative Office Building, 300 Capitol Ave., Hartford.
Lesley Bennett, part of NORD’s Rare Action Network and Connecticut’s Volunteer State Ambassador, organized the Hartford event. For more information, please email her at Lesley.bennett@rareaction.org.
Rare Disease Day – held annually on the last day of February – is a time to bring together doctors, researchers, advocates, patients, caregivers, industry representatives, and legislators in Connecticut and around the world to focus on the critical role patients play in understanding rare diseases and in developing innovative treatments and cures.
About 300,000 people in Connecticut have a rare disease. A disease or disorder is defined as rare in the United States when it affects fewer than 200,000 Americans at any given time, according to NORD.
Of the more than 7,000 rare diseases, NORD also says that 80 percent of rare diseases have genetic origins, while others are from infections (bacterial or viral), allergies, and environmental causes, or are degenerative and proliferative. Fifty-percent of rare diseases affect children.
Legislators and attendees will hear from Hope in Focus (formally Sofia Sees Hope) about patient access to treatment during the “Patient Issues” portion of the program.
The moderator for Connecticut’s event is Dominic Cotton, a Milford resident with 25 years of experience in behavioral healthcare management. He is a parent and an active advocate for rare diseases and brain injuries.
Rose Avellino, NORD’s Grassroots Advocacy Manager, will open the event. Avellino helps with the nationwide Rare Action Network and state policy issues.
Here is Thursday’s agenda, followed by a list of scheduled speakers:
8:30 a.m.: Opening Remarks
8:40 a.m.: Connecticut General Assembly Welcome
9 a.m.: Rare Disease Programs and Research
9:40 a.m.: Rare Disease Business in Connecticut
9:50 a.m.: Impact of Rare Diseases on Connecticut Families
10:15 a.m.: Legislative Issues
10:25 a.m.: Patient Issues
10:40 a.m.: Closing Remarks
Speakers (in the order in which they will be speaking):
Representative Joe Aresimowicz, CGA House Speaker, recently introduced legislation concerning continuing medical education in screening for rare cancers. He is one of the Rare Action Network’s Champions.
Greta Stifle, Neuroendocrine tumor (NETs) patient and advocate, is the founder and president of STIFLE Cancer Foundation, Inc. She is a Neuroendocrine Tumor & Mast cell patient actively advocating for patients with rare cancers through campaigns, such as the Zebra Project and the Neuroendocrine Tumor Awareness Campaign.
Senator Len Fasano, CGA Senate Minority Leader, recently introduced two bills to assist patients and families with developmental disabilities and helped make Connecticut become one of the first states to add Adrenoleukodystrophy (ALD) to the Newborn Screening Panel. He is also a Rare Action Network Champion.
Hunter Pageau, a patient and advocate, is a Rare Action Network Youth Champion. He was born with an ultra-rare motor neuron disease – Spinal Muscular Atrophy with Respiratory Distress (SMARD). Despite his own medical challenges, Hunter actively raises his voice to advocate for others who have rare, life-limiting illnesses.
Ching Lau, MD, Ph.D., is the Division Head of Connecticut Children’s Medical Center’s (CCMC) Center for Cancer & Blood Disorders and professor of Genomic Medicine at the Jackson Laboratory (JAX Labs). He specializes in finding new treatments for children with rare blood, bone, and brain cancers.
Charles Whitaker, MD, is a neurologist who sees patients at the Hospital for Special Care (HSC) outpatient clinic. He specializes in researching and treating adult neuromuscular disorders
Cristian Ionita, MD, is Co-Director of the Yale/MDA Pediatric Neuromuscular Clinic and Assistant Professor of Pediatrics (Neurology). His research focuses on pediatric neuromuscular disorders.
Saquib Lakhani, MD, is Clinical Director of Yale Medicine’s Pediatric Genomics Discovery Program (PGDP). He specializes in caring for newborns and infants with undiagnosed birth disorders.
Paul Pescatello is President and CEO of the New England Biotech Association and chairs the Connecticut Business & Industry Association’s (CBIA) Bioscience Growth Council.
Dan Donovan is Co-Founder & CEO of rareLife solutions. His passion for improving life for those with rare diseases is based on personal and professional experience.
Erica Mumm, DNP, MSN, RN, is a Clinical Assistant Professor in the Quinnipiac School of Nursing, and the mother of a child with a rare genetic disorder called KCNQ2 encephalopathy.
Alissa DeJonge is a caregiver, Vice President of Research, Connecticut Economic Resource Center, Inc., and the mother of a 2-year-old with severe hemophilia.
Heather Knapp is a caregiver and mother of four; her youngest child, a 2-year-old boy, was identified at birth in the state’s newborn screening program with Phenylketonuria (PKU).
Father Nikolas Karloutsos is a caregiver for his daughter who has a BRAF mutation Rasopathy – probably Cardiofaciocutaneous (CFC) Syndrome, which causes marked behavioral health/cognitive issues.
Jennifer Ianuzzi is the caregiver for her child with Smith-Magnis Syndrome, a developmental disorder caused by chromosome 17 microdeletions. Besides congenital abnormalities, this syndrome causes behavioral health and cognitive issues.
Guyla Acsadi, MD, Ph.D., is the Division Head of Neurology at Connecticut Children’s Medical Center (CCMC) and Professor of Pediatrics and Neurology at the University of Connecticut School of Medicine. He has a Ph.D. in Molecular Genetics and expertise in neuromuscular medicine.
Colleen Brunetti of West Hartford has pulmonary arterial hypertension (PAH) and actively advocates for patients. She is a board member of the Pulmonary Hypertension Association.
Representative Jillian Gilchrest is a House Representative from West Hartford. She introduced bills addressing co-insurance assistance programs needed to help patients afford prescription medications.
Rosanne Smyle is a staff member of the Sofia Sees Hope patient advocacy organization – a global non-profit dedicated to improving the lives of those affected by rare inherited retinal disorders that cause blindness.
Donna Sciacca is Community Outreach and Education Manager for the Connecticut division of the American Liver Foundation. She is responsible for patient education programs and raising public awareness of liver diseases. She also serves on the Board of Donate Life CT, an organ donation and transplant coalition.
Jecy Belmont of Hamden is a patient and an advocate with the rare bile duct disease, Recurring Primary Sclerosing Cholangitis, and had to have a liver transplant. Despite his own health issues, Jecy works tirelessly to educate the public on liver-related health issues.
Representative Fred Camillo is a House Representative from Greenwich who advocates for rare pediatric blood cancers. For the last two years he has held Donna Marie Camillo’s Paws For A Cause Walk to Cure Childhood Leukemia to honor his sister who died of a pediatric blood cancer.
Danielle Delgado, a patient and advocate, is a Rare Action Network Youth Champion. She has been diagnosed with two rare diseases (von Willebrand and Ehlers Danlos) and works to bring joy to other children who are ill.
The best of both worlds – that’s how Ashlyn Lincoln describes life with her two sons: 4-year-old Gunner, who was born without vision, and 7-year-old Ace, who is sighted.
“Both Ace and Gunner teach us many life lessons, regardless of who is sighted and who is blind,” says their 29-year-old mom.
7-year-old Ace and his 4-year-old brother Gunner. Gunner was diagnosed at 6 months with LCA10, caused by a mutation in his CEP290 gene. Doctors determined Gunner came into this world with no usable vision cells and no light perception.
Living in eastern Iowa, Ashlyn and her husband, Axel, noticed problems with Gunner’s eyes in August 2014, when he was about 2 weeks old: he stayed awake during the day and his eyes would not focus. The pediatrician examining their infant at 6 weeks wasn’t concerned, but to put them at ease, he referred them to the first in what would become a series of specialists, leading to lots of tests on Gunner’s eyes and on his parents’ genetic backgrounds.
Gunner was diagnosed with Leber congenital amaurosis (LCA) at 4 months; at 6 months in February 2015, his parents learned through genetic testing that he had LCA10, caused by a mutation in his CEP290 gene. Doctors determined Gunner came into this world with no usable vision cells and no light perception.
Last May, the family moved to a suburb of Nashville, seeking a stronger support system and better resources for Gunner, who is now thriving at the Tennessee School for the Blind.
Mr. Independent
Gunner loves prekindergarten, especially gym time and swimming lessons. He listens to try to understand musical instruments, and he loves making art and writing on the Brailler. “He’s pretty independent,” Ashlyn says.
Ace and Gunner have a typical sibling relationship, blaming each other, kicking each other, playing in their own world, she says. “Ace pretty much treats him like he is sighted. He adjusts (when he remembers Gunner cannot see) and goes right back to thinking it. It’s the best of both worlds.
“Their positive outlook and attitudes on life really help us be better ourselves. I just feel so lucky to be able to always have different outlooks on everything that others may not realize,” she said.
Gunner ‘reads’ his Braille books. Gunner’s reading is feeling the Braille but making up his own stories as he goes along.
Their daily life is like other families — the boys get up and get ready for school, eat breakfast, brush their teeth. After school they have snack, play, watch cartoons, do homework.
“This might be the only thing ‘different,’” Ashlyn notes “Ace’s homework is reading, so Gunner will bring his Braille books to the couch and ‘read’ them, too. Gunner’s reading is feeling the Braille but making up his own stories as he goes, which are usually pretty creative and cute.”
Ashlyn’s best-of-both-worlds might as well extend to a third “world,” given the influence, support, and love she and her family have received from Axel’s “battle buddies” from his time in the Marines.
War Wounds Inside and Out
Axel served four years’ active duty (followed by four years’ inactive duty), being deployed twice to Afghanistan and once to Haiti on a relief mission.
He came home from Afghanistan suffering from severe injuries when his right shoulder took the brunt of his Humvee’s impact after it ran over an IED, an improvised explosive device.
Axel and Ashlyn married as soon as they could after his return home. He has a 90 percent disability rating for the injury and for Post-Traumatic Stress Disorder (PTSD). About two years ago, Alex’s service dog, Tucker, became part of the family, helping with his PTSD and bringing comfort when his anxiety is high. Tucker’s also great with the boys and may someday be joined by a service dog for Gunner.
Axel wasn’t the only one to come home to the Lincoln family. The Marines came, too, and they are still part of it.
When Ashlyn was about to deliver her firstborn, her husband and his Marine friends were there. If the baby was a girl, she’d get to name her. If not, Daddy and his buddies had the honors.
“They gave me options. I had Achilles, Leonidas, Thor, Zeus – I was excited about that one.”
Achilles it was, or Ace, as they call their now first-grader.
It was Ashlyn’s turn to name their second boy, but she still wanted to honor their military family.
She explained that a gunner, sitting on top of a Humvee and rotating 360 degrees to protect its occupants, would throw himself on a badly injured compatriot as “an unwritten act of brotherhood.” The gunner in Axel’s case did not have to, but if Axel’s injuries were worse, he would have.
“So, to go along with the history of Ace’s name, we picked Gunner to name him.”
When she picked the name, she didn’t think much about looking up its meaning.
“Later on, after we got the diagnosis, I randomly decided to look up the meaning to find it meant ‘Battle Strong,’ which seems very appropriate on our adventure.”
You’re Overwhelmed and It’s OK
Life wasn’t always easy though. Dealing with Gunner’s diagnosis and coping with new realities was difficult. Here is the message she would like to extend to other mothers: “I was overwhelmed, and I was tired. I want to acknowledge that I know you’re overwhelmed and it’s OK.
“Take baby steps, know your local resources, and know that it’s not just something you’re going to conquer in one day.”
For support and to learn more about the LCA community, Ashlyn and a friend she met through an LCA Facebook group, traveled to Connecticut last fall to attend Hope in Focus (formally Sofia Sees Hope) LCA Family Conference, where she found a sense of community.
“It was fantastic,” she says. “There are families in other states and I’m not alone and here we are together. It’s just a moment where you can find comfort and know you’re not alone.”
Ashlyn said she does have a personal goal – one that she’s fulfilled right here.
“It’s hard to admit when your child is born and not perfect, and your husband has PTSD,” she said. “I hope that just by telling my story about LCA and veterans, that other families also can not feel so alone.”
The journey from identifying a rare disease, to conducting studies, to approving a treatment, is long – but it always starts with the patient, and the information patients share among the medical, biotechnological and advocacy communities, as well as within the patient community.
At a fall gathering of families living with Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs), Lisa Bernier found help and support for her visually impaired daughter for the first time in seven years. Bernier and her 25-year-old daughter, Aimee, traveled to the first-ever Hope in Focus (formally Sofia Sees Hope) LCA Family Conference at the insistence of Aimee’s optometrist.
“Advocacy ends after school ends,” Bernier says.
Lisa and Aimee Bernier
Aimee has Bardet-Biedl Syndrome (BBS), a complex disorder affecting many parts of the body, including the retina. She and others with BBS have retinal degeneration similar to retinitis pigmentosa (RP). Aimee had good experiences at the Perkins School for the Blind and graduated in 2011. Then it became difficult for her mother to find support.
“We’re basically on our own, to advocate for ourselves,” Bernier says. Her 30-year-old son also has BBS with many, but not all, of the same characteristics, and his vision loss is five years’ advanced.
(Editor’s note: Laws vary from state to state, but typically, public education is required to provide services to students in need until age 21, even after high school graduation. Children with learning disabilities who receive services under the Individuals with Disabilities Education Act (IDEA) or the Rehabilitation Act of 1973 (RA) in public elementary and secondary school may continue to have legal rights under federal laws in college programs and in employment. When students graduate from high school or reach age 21, their rights under the IDEA come to an end. As resources can vary greatly from state to state, finding support and resources for a child may fall on the family post-graduation.)
During the early years, Bernier searched for any information on BBS and RP through reading the New England Journal of Medicine, which described those with BBS as having low cognitive skills and dying from kidney failure. Even when Aimee was born, the doctors didn’t understand BBS. Bernier and her husband were grateful to be introduced to the doctors and genetic staff at Shriners Hospitals for Children in Springfield, Mass., where they helped with the health care needs of Aimee and her brother until they were 18.
Bernier said she was thrilled to be at the conference in a roomful of retinal experts, patient advocates, and families attending the Oct. 6 gathering.
More than 50 people from New England, across the country and Mexico attended the conference, including the session titled “The Role of the Patient Voice in Developing Treatments for Rare Disease.” Sofia Sees Hope Executive Director Annette Tonti moderated a three-member panel comprised of:
• Jamie Ring, Head of Patient Advocacy at Spark Therapeutics, which developed the gene therapy called LUXTURNA™ that helps restore vision to people with RPE65 genetic mutations;
Jill Dolgin
• Jill Dolgin, PharmD, Head of Patient Advocacy at AGTC, a clinical stage biotechnology company focusing on rare IRDs and developing therapies that replace “broken” genes with normal, functional genes;
• Kristen Angell, Associate Director of Advocacy at NORD, a voice for the 30 million Americans with rare diseases and the official U.S. sponsor of Rare Disease Day, which takes place annually on the last day of February.
Personal experiences of family and/or friends dealing with rare diseases motivated all three women to become advocates for patients. As Angell paradoxically put it: “Rare disease has always been common in my family.”
Ring, Dolgin and Angell are a critical part of a relatively new profession – patient advocacy – to help people find support and learn how to become engaged in the process of drug development and research to find treatments for rare diseases.
Kristen Angell
Ring from Spark Therapeutics said she has a passion for helping amplify the voices of the patients and their families and making sure those voices are understood and considered.
“People feel their story doesn’t matter,” she said. “The thing in rare disease is that YOU ARE the expert,” and patient information is critical to doctors and biotechnology companies alike. “At Spark, we want to make sure that patient voice has a seat at the table.”
Connections and Clarity
“There’s no one-size-fits-all,” Ring said. “Simply connecting with other people is probably the most important thing you can do … and having the clarity of your diagnosis allows you to do that most effectively.”
For IRDs, it is essential to know your gene and it’s a good idea to register with My Retina Tracker, a confidential, online, patient registry managed by the Foundation Fighting Blindness. Patient data tracked through registries and collected by researchers helps scientists and biotechnology companies develop clinical drug trials.
AGTC’s Dolgin told the audience that 7,000 rare diseases exist, but fewer than 15 percent have advocacy groups that can assist patients with resources, advocate for clinical research, and find access to vital therapies.
Dolgin, a trained pharmacist, emphasized: “As patient advocates in the pharmaceutical industry, we’re representing the patient at the corporate table.” A priority for the company is to find and educate people with IRDs and encourage them to get genetically tested.
Patients need to be identified, encouraged to enroll in natural history studies, and followed systematically through natural history studies long before beginning the clinical drug trials necessary to seek approval for commercial use from the U.S. Food and Drug Administration. Natural history studies are critical components to clinical research, providing an understanding of the rate of disease progression without treatment to the rate of disease progression after treatment.
Angell said NORD developed 20 patient registries for 20 different diseases in the last few years. She oversees the Rare Action Network, with 5,000 members nationally and ambassadors in 32 states, including Connecticut. The network empowers patients and families to directly reach out to lawmakers to encourage and support the rare disease community.
Angell also encouraged using social media and suggested setting up programs with local chambers of commerce to make people aware of patients in their own community.
“Awareness goes hand in hand with advocacy.”
Shared Experiences & Knowledge
The role of the patient voice continues even more so after development of a treatment. Ask the people with families living with LCA. Sofia Sees Hope has been working to connect these families who have similar concerns and many of them have supported one another and become friends.
She’s had many conversations with people involved in the process of LCA treatment or are hopeful they might be involved in a future clinical trial. The first person she talked with was Sarah St. Pierre Schroeder, the mother of now 10-year-old Creed Pettit. They communicated last April on the eve of the boy’s surgery in which doctors at Miami’s Bascom Palmer Eye Institute would inject under his retina a human-engineered virus that gives instructions on how to produce an essential protein for vision.
“I kept thinking about her and Creed in the days prior to Creed’s procedure,” Morehouse said. “I remembered how I felt when I was in their shoes and couldn’t help but reach out to them on the night before Creed’s procedure. As it turned out, Sarah seemed very open and happy to talk with someone who had been there and understood a little about all that they were feeling and wondering about.”
Creed’s mom felt enormous relief in talking with Morehouse.
“I will never forget the emotions I felt when Tami reached out to me,” St. Pierre Schroeder said. “Every sentence in her email brought me more comfort about what I was doing for Creed. She was so open about her journey, I felt like we had known each other forever.”
LUXTURNA took decades of research, many millions of dollars and countless advocacy connections to come to fruition. It is a long journey that begins with the patient and comes full circle.
Dr. Maguire is part of the married research team that brought the genetic therapy treatment developed by Spark Therapeutics called LUXTURNA™ to fruition. Dr. Jean Bennett and Dr. Maguire researched and conducted studies working with mice and dogs, and then humans in clinical trials. They developed the first genetic therapy treatment for LCA2 (RPE65), and the first treatment in the United States for any inherited disease. The U.S. Food and Drug Administration approved it in December 2017.
Hannah had a milder form of LCA, with night blindness and poor peripheral vision. Her mother, Amy, still marvels at the idea of genetic research focusing on her daughter’s gene mutation.
Using a syringe, Dr. Maguire injected under Hannah’s left retina a human-engineered virus containing a healthy version of the gene, which supplants the mutated gene. Within 24 hours of the July 10 surgery, Hannah had increased sensitivity to light; six days later, she could see the water line in her glass, rather than sticking her finger in the glass to feel for the water. On Day 7, she saw a star for the first time; six days later she underwent surgery on her right eye.
‘She can see’
Hannah can now see everything in her environment more easily and her visual acuity has improved from 20/200 to 20/100.
Shortly after surgery, Hannah flipped on her desk lamp and was so startled by the brightness that she began to cry. Now, Hannah says, “I don’t even remember what it was like before my surgery.”
Amy and her husband, Chris, revel in their little girl playing with her horse figurines in a dark room on a cloudy day, and they say her night vision has improved a thousand-fold.
8-year-old Hannah Reif of Maple Glen, PA.
“It’s just wonderful to watch her do things and see things. She’s not saying, ‘Hey, look what I’m doing.’ She just does it. She can see.”
Her mom said most recently, she’s just discovered the blue veins under her skin and the “H” and “C” on the bathtub faucets.
Her parents and others have noticed she’s more confident in school, in church and socially with her friends. Although she still needs some supports in place at school, Hannah’s doing great in her second-grade class.
On past Christmas mornings, she’d open a gift and have to be told what it was. Not this year!
Amy also recalled Hannah walking into their church sanctuary, brightly decorated for Christmas with ribbons, greens and flowers.
“As she walked through the doors, she looked around in amazement and said in a soft, sweet voice, ‘Wow!’ ”
‘Like night and day’
Kindergartener Monroe Le underwent surgery Aug. 14 on her left eye and a week later on her right eye.
“She’s like night and day,” said her mom, Heather.
Before surgery, Monroe’s vision was 20/300 for both eyes and now it’s 20/150.
So much has changed since 2012; Heather knew something was wrong with baby Monroe at 2 weeks when she looked toward the light rather than her.
6-year-old Monroe Le of San Diego, CA.
“I remember crying and saying to my husband, ‘She’s blind. She’s blind,’ and he said, ‘She’s not’ … from 2 weeks until she was diagnosed, we were knocking on doctors’ doors.”
Heather was scared to have her daughter genetically tested, but she knew it would give her answers. Doctors diagnosed Monroe with LCA shortly after she turned 4; two months later she received her RPE65 genetic diagnosis.
“Oh, I’m so happy that I did it,” Heather said. “If I hadn’t gotten that test, Monroe wouldn’t have been a candidate for LUXTURNA.”
Her daughter received help to get up to speed with motor skills, and early on met a little girl named Penny, her forever friend, who has had difficulties with speech.
“They’re amazing, they love each other so much,” Heather said. “They complemented each other so well because Monroe would help her with the talking and Penny would help her with the seeing.”
Two days after her first surgery, Monroe insisted on being the one to retrieve a cap from an ointment tube dropped on the carpet. “She covered her non-surgerized eye and found it immediately.”
In school, Monroe no longer needs special lighting and doesn’t have to sit in the front of the room. “She even has been able to play four square.”
Monroe also sees her most favorite place in the world, Disneyland, and her most favorite attraction – Pirates of the Caribbean with Capt. Jack Sparrow – in a whole new light.
“There have been numerous times in a trip there where she asks me, ‘Mama is that new, or has it always been there and I’m just seeing it for the first time?’ ”
Heather and her husband, Bruce, see a much more confident little girl who no longer needs to hold hands in dim places.
“I can’t believe it’s the same girl who was so timid and afraid to let go of my hand,” she said.
The lack of information on rare diseases can create difficulty in developing drugs to treat them. To help, it is important to study the natural history of rare diseases.
Compared with common diseases, researchers know little about rare disease signs and symptoms, how the disease changes over time, and ways in which the disease affects the lives of patients and their families.
Natural History studies track the course of a patient’s disease over time. They identify demographic, genetic, environmental, and other variables that shape the drug development process
Dr. Eric Pierce, Massachusetts Eye and Ear
“In general, Natural History studies can be helpful precursors to clinical trials of potential treatments for inherited retinal degenerations for multiple reasons,” said Eric A. Pierce, MD, Ph.D., with Massachusetts Eye and Ear. “For example, they can help identify the tests or measurements which would be most appropriate to use as endpoints in therapeutic studies.”
Another way to view such studies is to “Begin with the end in mind,” as suggested by Anne R. Pariser, MD, in her work on Natural History studies for the U.S. Food and Drug Administration
Natural History data provide knowledge and an independent understanding of a disease, while establishing an essential foundation for building drug development programs. These studies have been characterized as the “pillar of epidemiologic research on rare conditions,” and, along with assisting in developing drugs, they help with patient care, best practices, research priorities, and clinical trial readiness, according to Dr. Pariser, director of the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences.
The studies give scientists and researchers a better estimate of the prevalence of the disease, help identify potential biomarkers, affect clinical outcome assessments, and determine the feasibility of established assessments for clinical trials.
A rare disease is a disease or a condition that affects fewer than 200,000 Americans. With a relatively small number of people affected by the 7,000 diseases considered rare, scientists sometimes face daunting odds in finding enough people meeting study requirements.
In the Leber congenital amaurosis (LCA) community, scientists are looking for people to take part in different stages of drug development.
Editas Medicine, a genome-editing company based in Cambridge, Mass., is sponsoring a Natural History study of LCA10, known by its gene name CEP290, to inform the design of potential future treatment studies involving genome editing in LCA10. The purpose of the study is to understand and better describe the clinical course of LCA10-related retinal degeneration that is associated with a particular genetic change in the CEP290 gene called c.2991+1655A<G.
The study will be used to characterize the range of visual function in patients, evaluate which visual tests may be most useful, and determine the rate of change in visual function over a one-year period.
Dr. Pierce, director of the Ocular Genomics Institute and the William F. Chatlos Professor of Ophthalmology at Massachusetts Eye and Ear (MEE) and Harvard Medical School, is the principal investigator at one of the seven sites in the United States and Europe actively recruiting patients for this Natural History study. For more information, call MEE at 617-573-6060 or visit www.enlightenLCA10study.com/. Study details also can be found at ClinicalTrials.gov Identifier: NCT03396042.
The two groups of conditions below describe the parameters for taking part in the study. Taken together, they illustrate the potential difficulty in finding the 40 participants needed for the study of this rare disease.
Patients must meet six conditions, known as inclusion criteria:
3 years of age or older;
Abnormally decreased vision, with examination and test results consistent with inherited retinal degeneration due to mutations in the CEP290 gene;
Able to cooperate with assessments relative to the patient’s age;
Clear ocular media and adequate pupil dilation in at least one eye to permit good-quality examination of the interior surface of the eye opposite the lens and optical coherence tomography (OCT) imaging;
Able to successfully navigate a mobility maze at a level of difficulty below the maximum performance level.
Patients cannot participant if one or more of the five following conditions, called exclusion criteria, exist:
Visual acuity of no light perception in both eyes;
History or current evidence of a range of medical conditions that may preclude attending scheduled study visits, safe participation in the study, or affect the study results;
History or current evidence of ocular disease in either eye that may confound assessment of this inherited retinal disease;
Currently receiving gene therapy and/or has received gene therapy;
Currently enrolled in an investigational or interventional drug or device study and /or has participated in such a study within 30 days of screening.
Participants currently are being recruited for a Foundation-funded Natural History study of disease progression in patients with USH2A-related retinal degeneration associated with congenital hearing loss (Usher syndrome type2a) or non-syndromic retinitis pigmentosa (RP39).
“I feel that there are a lot of parents out there that are terrified for their kids to live this life,” she says from her southeastern Texas home. “And while it’s not ideal, it doesn’t mean that they aren’t capable of living a fulfilled life and love it like they should.”
Larson’s form of LCA, known as LCA6 caused by a mutation of the RPGRIP1 gene, is considered rare even within the realm of rare disease, accounting for only about 5 percent of the total LCA patient population. LCA in its more than two dozen genetic mutations affects fewer than 4,000 people in the United States; it accounts for 5 percent of all retinal dystrophies and 20 percent of blindness in school-age children.
Photoreceptors lacking RPGRIP1 are unable to maintain the retina’s light-sensing outer segments, resulting in patients losing retinal functions at an early age but retaining photoreceptors in the central retina well into adulthood, according to the National Institutes of Health.
Having grown up with vision loss, Larson says children born with LCA need the support of knowing that others have gone through life with the same inherited retinal disease and survived the bullying, mistreatment or embarrassment.
“I think I’d tell any parent that getting their child into therapy is a necessity,” she says. “Most of us need help navigating these very important emotional things in life. Like when you get made fun of, or when your sibling or friends get their driver’s license and you can’t. Just coping with what this will mean for their life and how to navigate it.”
Larson speaks from experience. More than anything, she wants to take the element of pity out of dealing with the disease.
“It does no good to have pity, or on the other side, to put people on a pedestal for doing things everyone can do,” she says. “It’s demeaning and degrading as a human to get praise for doing something everyone else can do, just because we can’t see well.”
She has some light perception and equates her field of vision to about the length of a drinking straw. With lenses, her visual acuity is 20/200 and 20/400.
Larson had vision loss early and began learning Braille at age 4. She was diagnosed at age 12, although incorrectly, with Retinitis Pigmentosa (RP). She worked with specialists to improve her independence but being around other kids never was easy. She was teased.
“You need extra help. You don’t want to stick out,” she recalls. “I made myself want to fly under the radar.”
By middle school, she didn’t want to deal with Braille or learn more about skills and concepts to help her get around and to be more independent.
“It was something that I just despised. I don’t want to be identified that way. I don’t want to be that kind of person.”
Larson did, however, go to Arizona State School for the Deaf and Blind in Tucson for her last two years of high school, graduating in 2007. She pursuing job training through the state’s Vocational Rehabilitation (VR) services, but the program lacked funding and was not accepting new clients.
While on the VR program waiting list in 2008, she met Andrew, who is now her husband, and in 2009 became pregnant with their first child.
Mikayla and Andrew Larson
They married in 2011, when their first-born, Conner, was 1. The day after the wedding, she was pregnant with her little girl, Aubrie. They lived outside of Phoenix and then moved even farther from family, southeast to a small Arizona town for Andrew’s first job as a chemical engineer.
The family moved in 2013 to another small town in southeastern Texas.
She is the mother of four children, “three here and one in heaven.” Their son Liam died from Sudden Infant Death Syndrome on April 3, 2015. He was 4 months old.
“My kids are very independent,” she says of 8-year-old Conner, 6-year-old Aubrie and Carter, 5. “They get up on their own with an alarm and get themselves dressed, and then Andrew and I make breakfast and make sure they have brushed teeth and are ready for school.”
Not being able to drive is a big deal, especially in rural Texas with no public transportation. Her children are picked up for school and driven home. Cooking has gotten easier and more comfortable with the advent of Air Fryers and Instant Pots.
Tripping over toys and three cats – Max, Teddy and Chester – is part of life. She shops with family and reads with the help of reading glasses and her phone’s camera, zooming in for small print.
“I would say I’m pretty self-reliant and just do what I need without any real thought.” She does suffer from anxiety.
“Once we lost Liam, the anxiety kind of crossed over into other parts of my life.” She is seeking help and open to resources.
Her biggest advocate, Andrew, contacted Spark Therapeutics, the developer of a new gene therapy called LUXTURNA™ for LCA2 (RPE65) because he thought she might have that form of LCA. The company suggested she receive genetic testing.
When Larson visited an ophthalmologist for a genetic testing referral, she was met with disbelief. The doctor said she couldn’t have LCA. “It’s too rare. That’s not possible,” he told her.
She finally got the doctor’s signature for testing, and, in January 2017 at age 28, her test revealed a mutation in her RPGRIP1 gene, also known as LCA6.
Larson says she was then in touch with Eric Pierce, MD and PhD, who is conducting lab-based research on RPGRIP1 at Massachusetts Eye and Ear. Dr. Pierce’s gene research involves evaluating the latest treatment version in a mouse model, with the plan to generate a gene-therapy vector for toxicology studies, ultimately leading to clinical trials.
While hopeful for a treatment, Larson prides herself on helping others and moving forward.
“We are still smart and capable. We have different challenges but that doesn’t mean we aren’t able.”
