CHOP Researchers Developing Database to Speed MLD Diagnosis

CHOP researchers have received funding to better diagnose and treat patients like Taleen, 7, who is affected by a rare brain disease called metachromatic leukodystrophy. (Photo courtesy of the Soliman family.)

Researchers at Children's Hospital of Philadelphia are creating the world's largest database for clinicians to more quickly diagnose metachromatic leukodystrophy (MLD), a rare childhood brain disease.

"I hope this grant helps us to understand a complicated and devastating disease," said Laura Adang, MD, PhD, MSTR, an attending physician in the Division of Neurology who specializes in the care of children with leukodystrophies.

At CHOP's Leukodystrophy Center, Dr. Adang and her research team have spent nearly a decade analyzing medical records to better understand rare, progressive childhood diseases, including MLD.

Their new tool, MLD-CORE Project, will go a step further. Funded by the National Institutes of Health, the diverse database will "harmonize" lifelong medical record data from hundreds of patients across a network of leukodystrophy centers. The goal is to establish the world's largest natural history study of children affected by MLD.

Leukodystrophies are inherited diseases that damage myelin — the protective covering around nerve fibers — slowing or blocking communication between the brain and the body. MLD is a progressive disease that affects about one in 40,000 individuals in the United States. Most children quickly lose the ability to walk and talk, and the disease is usually fatal within 10 to 20 years of diagnosis.

Laura Adang, MD, PhD, MSTR

While a gene therapy to treat MLD was approved in 2024, it is most effective when given before permanent damage occurs, and not all subtypes of the disease qualify for it. That's why it is critical to know exactly who is most at risk for MLD and what the progression of their individual disease subtype might look like, Dr. Adang said.

"Right now, we know only a limited amount about how MLD begins," Dr. Adang said. "In our study, we are collecting information from birth to present day. A child may not have been diagnosed with MLD for three years, but we will still go back in the records and extract every single important piece of information prior to that."

The researchers' hope is to pick up on the subtle, early hints about MLD that could one day inform guidelines for future patients. Additionally, the information will be crucial for researchers developing and enrolling patients into clinical trials for new MLD treatments.

By 2026, MLD will be added to Pennsylvania's newborn screening panel, an addition that Dr. Adang helped to champion. However, due to the diversity of disease subtypes, children can still go many years without receiving proper diagnosis or care.

"MLD tends to present in very subtle ways," Dr. Adang said. "By the time most children are diagnosed, it can be too late for treatment."

The medical community's understanding of the disease has largely derived from single institutional reports — a siloed research approach that has slowed scientific progress, she added.

"My goal is that this tool will help us better serve our newborn screening population — to reduce the ambiguity of results," Dr. Adang said, "but also to help develop future clinical trials that will include many more MLD patients, because right now our entire population is not being served."