By Marc Shapiro
Thanks to the efforts of clinician-scientists and advocates, including one of Kennedy Krieger Institute’s own faculty members, a devastating genetic disorder called metachromatic leukodystrophy (MLD) was recently added to the federal list of recommended newborn screenings.
MLD affects the brain, spinal cord, and peripheral nerves. It often develops in the first year of life. Without early disease detection and gene therapy, children with the condition slowly lose the ability to walk and speak, and eventually to move, swallow, and breathe, succumbing to the disease by 4 or 5 years old. MLD, usually caused by a missing or deficient enzyme, affects one in 100,000 newborns per year in the U.S.—about one baby every week.
In December 2025, Dr. Eric Mallack, director of clinical research at Kennedy Krieger’s Moser Center for Leukodystrophies, provided a congressional briefing at the U.S. Capitol on MLD, speaking about how the disease can be detected with a simple blood test and prevented with a new gene therapy if administered before symptoms appear. Later that month, MLD, along with Duchenne muscular dystrophy, was added to the Recommended Uniform Screening Panel (RUSP) for newborns.
“There is no other therapy across medicine that has fundamentally changed the natural history of a neurogenerative disease like this in history,” Dr. Mallack says. “With this gene therapy, children can develop, go to school, and go on to live their lives. Newborn screening makes that possible.”
Dedicated to Saving Lives
The term “leukodystrophy” is used for a group of rare genetic diseases that lead to abnormalities in the brain’s and/or spinal cord’s white matter, which facilitates nerve communication. More than 40 leukodystrophies have been discovered, and they are often fatal.
The Moser Center, one of the most comprehensive leukodystrophy centers in the U.S., is named for the late Dr. Hugo Moser, former Kennedy Krieger president and one of the world’s foremost leukodystrophy experts during his lifetime. Ann Moser, his wife, is a research associate in neurology at Kennedy Krieger. She continues their research and advocacy in adrenoleukodystrophy (ALD), a disorder similar to MLD that harms the nerves in the brain and spinal cord. In 2015, thanks in part to the Mosers’ work, ALD was added to the RUSP. As of today, 48 states and Washington, D.C., screen all newborns for ALD.
Everyone at the Moser Center … is dedicated to this group of rare disorders.” – Dr. Eric Mallack
Delivering Novel Treatments
In addition to providing clinical care, Dr. Mallack uses advanced MRI techniques to understand brain development, predict disease onset, monitor disease progression, and understand treatment effectiveness in patients with leukodystrophy. Together with his team, in partnership with The Johns Hopkins Hospital, he has developed a program for neurogenetic therapies—“interventional neurogenetics,” as he describes them—to address this devastating group of disorders.
Therapeutic approaches for MLD include delivering the missing enzyme directly to the fluid surrounding the spinal cord and brain. Bone marrow transplants show promise for patients with ALD, and for those with Krabbe disease, another type of leukodystrophy. For individuals with adult polyglucosan body disease, a type of leukodystrophy that shows up in adults, a novel drug called an antisense oligonucleotide (ASO) improves impaired gene expression. Dr. Mallack serves as principle investigator for multiple clinical trials, including the first oral therapy for children and adults with the cerebral form of ALD.
“Everyone at the Moser Center—the residents, the faculty, the nurses—is dedicated to this group of rare disorders,” Dr. Mallack says. “That makes the Institute a really special place, and having that level of commitment really advances care.”
Above: Ayden, a patient at Kennedy Krieger, with Dr. Eric Mallack