‘Patients Are The Key’
Families, Researchers Share Insights at Rare Disease Day
Photo: NCATS
For the 30 million Americans who suffer from a rare disease, finding answers is personal and urgent. Many people with rare diseases first endure a long and complicated journey to get an accurate diagnosis. If and when they receive one, that complex journey isn’t over. For most rare diseases, few if any treatments exist.
“We at NIH believe that caring for people with rare diseases is at the heart of everything we do, because NIH can be a focal point for this incredibly diverse and challenging community,” said NIH Director Dr. Monica Bertagnolli during Rare Disease Day at NIH recently.
More than 2,200 people registered from around the world, many of them watching the day’s presenters via videocast. The annual event, held in the Natcher Conference Center, is sponsored by the National Center for Advancing Translational Sciences (NCATS) and the Clinical Center.
Photo: NCATS
This year’s presentations highlighted new models for developing treatments; a new FDA-approved drug for Duchenne muscular dystrophy; and the promise of data science and personalized strategies to accelerate the arrival of new therapies.
An often-repeated theme is the integral role of people with the disorders. As NCATS Director Dr. Joni Rutter said in opening remarks, “Stories from patients and families are the thing that guide our scientific journey and spur the meaningful change that we need to see.”
Patient and Caregiver Odysseys
Ashley Eakin’s journey has taught her the importance of visibility. She held off pursuing her dreams of being a filmmaker for years because she thought the career was out of reach for a person like her.
Photo: NCATS
Eakin has a rare condition called Maffucci syndrome, which causes genetic mutations that affect the growth of long bones and may also cause tumors. She has had more than 28 surgeries over her lifetime and has beaten ovarian cancer twice.
“I was ashamed of being different for most of my life,” she said. A speaker with a visible disability in a film business class in college changed her mindset.
Another lesson in inclusivity came later, when she worked as a director’s assistant for Jonathan Chu on the film Crazy Rich Asians. Eakin saw what the representation meant to the Asian community and realized that her shame about her own disability could stem from a lack of representation. She struck out on her own as a director in 2017 and has focused on projects that feature authentic characters who have disabilities.
“Go toward fear and face it,” she said. “It could change your life.”
Clinical Trials Crucial
Photo: NCATS
Dr. Dominique Pichard has devoted her career to rare disease research and advocacy, inspired by personal experience. Her daughter Catalina lost verbal language as a baby. Pichard suspected Rett syndrome but was immediately dismissed by the pediatrician.
“I was not seen; I was not heard. But in my gut, I knew I was right,” said Pichard, director, Division of Rare Diseases Research Innovation (DRDRI) at NCATS.
As a clinician, she knew her way around the medical system. She got referrals and met with specialists. Yet it still took a year to confirm that diagnosis. “[DRDRI] works really hard so that, one day, families don’t have to go through this.”
Catalina is now a teenager. For most of her life, no treatments existed for Rett syndrome—until now. Last year, the FDA approved a treatment, the culmination of more than a decade of clinical research.
Pichard reiterated her gratitude to clinical trial participants. “Patients are the key to finding treatments for rare diseases.”
Understanding, Empathizing Important
Jessica Swanson shared her family’s diagnostic journey, which took more than nine years. She knew of their family’s genetic predisposition to spinocerebellar ataxia, but tests revealed that wasn’t the cause of her daughter Isla’s spasms and relentless seizures.
Isla began displaying unusual movements at seven months old. When she was three, a medication tested during a clinical trial stopped her seizures, but the uncertainty continued without a diagnosis.
Photo: NCATS
“The challenge of conveying years of medical history in mere minutes to new doctors, the weight of the four-inch medical binder, and the trust placed in new hands never got easier,” recounted Swanson.
In 2021, the family connected with NIH’s Undiagnosed Diseases Network (UDN). A year later, a diagnosis arrived: CDKL5 deficiency disorder.
The diagnosis “provided a label, a community and hope for the future,” Swanson said. “With exciting medical treatments in the immediate pipeline, we would have missed the opportunity to improve Isla’s life because we didn’t have that diagnosis until the UDN.”
Swanson urged researchers, clinicians and advocates to take Isla’s story as a call to action.
“The need for a unified medical system and more collaborative approaches to patient care is evident,” she said. “Our experience underscores the importance of not just looking, but seeing; not just testing, but understanding; and not just treating, but empathizing.”
Finding New Treatments
Of the more than 7,000 known rare diseases, only a few hundred have active research programs, leaving a significant gap in available treatments. Investigators like Dr. James Hickman want to change that by developing new platforms for rare diseases.
Photo: NCATS
The co-founder and chief scientist for Hesperos, Inc., Hickman spoke about his company’s work creating custom, human tissue chip models to reproduce and develop treatments for a wide range of rare and ultra-rare diseases. Using cells derived from patients, he and his team create interconnected, multi-organ models that accurately reproduce specific disease states and a patient’s response to treatment. These models can predict patient outcomes more accurately than traditional animal models and are actively accelerating rare disease treatments today.
Hickman emphasized that these tissue chips “aren’t just laboratory things you might have in 10 years.” The various disease models he showed in his presentation are all commercially available.
Hesperos was the first company to enable authorization of a clinical trial using only data from a tissue chip model (NCT04658472). The drug was repurposed from another indication to treat chronic inflammatory demyelinating polyneuropathy/CIDP, a rare autoimmune disorder.
Hickman also empathizes with rare disease patients on a personal level; he has struggled with an undiagnosed peripheral neuropathy for 15 years.
“These [tissue chip] systems create hope for all patients battling a rare disease,” he said. “As the technology continues to gain adoption, we expect therapeutic development to continue accelerating for this underserved population.”
Promising research continues through the NIH-funded Rare Disease Clinical Research Network, which connects scientists to rare disease organizations and advocacy groups, and through the public-private Accelerating Medicines Partnership Bespoke Gene Therapy Consortium. Developments are on the horizon.
Expanding Access to Care
In a disadvantaged border town in Texas, a collaborative project gives hope to children with rare diseases and serves as a model that could be replicated and expanded.
Photo: Credit NCATS
Dr. Seema Lalani, a professor at Baylor College of Medicine in Houston, discussed the NCATS-funded Project GIVE (Genetic Inclusion by Virtual Evaluation), which enrolled about 100 families in the Rio Grande Valley (RGV). The medically underserved population there is largely Hispanic, living below the poverty line, with limited access to specialized care. Houston, where Lalani works, is five hours away.
“Reducing health disparities and improving access to care in RGV is a priority for us because these are children who have endured years of health decline with no prospects of preventing late morbidities and chronic diseases,” Lalani said.
Launched in 2022, Project GIVE used consultagene.org, a virtual platform designed by Baylor, to enable doctors to refer local Latinx children and provide families a tool for genetic evaluations.
Assisted by a bilingual social worker, the children gave biosamples at the study site, a clinic at the University of Texas-RGV. The clinic had a kiosk where families could subsequently go online for consultation and follow-ups with Baylor researchers.
So far, 61 families received genome sequencing results and 17 received diagnoses. Surveys revealed the families understood the genetic results and believed doctors would use those results to improve their child’s health.
For millions of people, the journey continues. Earlier, Swanson said, “The rare disease community taught us rare does not equate to alone; there is strength in shared experiences.”
“We are not done,” Bertagnolli pledged. “We have so much more to do. And we will continue to look for ways to work with everyone it takes as research partners to make life better.”
Photo: NCATS