By Laura Thornton
Finding the genetic cause of a patient’s seemingly unique set of symptoms can be like searching for a needle in a haystack. But for Julie Cohen, director of genetic counseling services at Kennedy Krieger Institute, it’s her job.
“Connecting patient cases with a gene can take years and span continents and is a very labor-intensive process, but it’s the first step toward improving patient care through genomic medicine,” she says. “When we can link a gene variant with a rare disease and correlate that with clinical outcomes, we can begin to tailor treatments to individual patients, offering hope to them and their families.”
The National Institutes of Health defines a rare disease as a condition affecting fewer than 200,000 people in the U.S. But many rare diseases affect only a few hundred—sometimes only a few—people worldwide, which can make learning about a rare disease very difficult. Researchers need to study as many patients with a disease as possible to determine the progression of the disease, how it affects people, and what treatments will work best.
For that, “International collaboration is critical,” says Dr. Ali Fatemi, the Institute’s chief medical officer and director of the Moser Center for Leukodystrophies. “When it comes to studying rare diseases, these are multinational efforts.”
Cohen and the Institute’s other genetic counselors see patients who typically have been experiencing symptoms for some time but who don’t have a diagnosis. Cohen and her colleagues order genome sequencing—of which Kennedy Krieger was an early adopter—to study a patient’s DNA. If they find a piece of DNA with a genetic change that doesn’t correspond to a known diagnosis, they use GeneMatcher.org, developed at Johns Hopkins Medicine, to see if anyone else from around the world has identified a patient with the same genetic change. Following this global approach, Cohen and her colleagues have uncovered—or helped uncover—more than 40 rare diseases, some affecting only a handful of people.
“We’re diagnosing patients who’ve gone undiagnosed for decades, as well as very young children,” she says. “Internationally, we’re at the forefront of this work.”
Given how rare some of the muscular dystrophies are, the only way to recruit enough people to complete a trial of a new treatment is to recruit from around the world.” – Dr. Doris Leung
Rare Disease Research and Clinical Trials of Treatments
Kennedy Krieger also plays an outsized role in conducting studies on the progression of rare diseases, and clinical trials of treatments for those conditions, thanks to its heavily concentrated expertise in rare diseases, treatments and clinical trial protocols.
“Kennedy Krieger’s tradition of developing clinics specifically for rare diseases gives specialists the opportunity to observe the full spectrum of disease and gain insights into the variations of diseases that we couldn't get from seeing only a few patients,” explains Dr. Doris Leung, who directs the Institute’s Center for Genetic Muscle Disorders.
But with so few people diagnosed with any given rare disease, data collection must be conducted on a global scale to ensure enough study participants.
“Given how rare some of the muscular dystrophies are, the only way to recruit enough people to complete a trial of a new treatment is to recruit from around the world,” Dr. Leung explains.
To collect information on the progression of Sturge-Weber syndrome, which can cause epilepsy and seizures, Dr. Anne Comi, director of the Institute’s Hunter Nelson Sturge-Weber Syndrome Center, worked with clinician researchers in different states and countries to collect data on the condition. “The collaboration was crucial in gathering comprehensive data and insights into the condition,” she says.
In 2024, Dr. Comi, along with her team members and other research partners, announced a new treatment protocol for the syndrome. Clinical studies supporting that protocol were also conducted on an international scale, and she now helps international collaborators implement the new treatment protocol worldwide.
“The international scope not only creates more generalizable outcome measures and biomarkers, but also brings in specialized expertise from outside the U.S.,” adds Dr. Jacqueline Harris, director of the Epigenetics Clinic at Kennedy Krieger. Dr. Harris leads an international collaboration collecting information on Kabuki syndrome, a genetic neurodevelopmental disability syndrome.
The international approach also helps spread Kennedy Krieger expertise around the globe, helping clinicians, patients and families far beyond Maryland and the U.S., and fueling an impact that knows no bounds.