Leukodystrophy Center Advances Early Diagnosis, Treatment, and Understanding

Leukodystrophies are a diverse group of rare, inherited disorders that affect the white matter in the brain and the spinal cord, resulting in developmental regression and premature death. Although these diseases do not currently have cures, if detected early — such as in the newborn period, prior to symptom onset or very early in the disease course — a stem cell transplant may be a therapeutic option for some patients. Early detection also allows for preventive care strategies to improve quality of life for children and their families.

Just 40 years ago, many of the leukodystrophies had not even been described and nothing could be offered in the way of treatment for those afflicted with these devastating conditions. Today, children can be diagnosed with once unimaginable precision and can potentially be candidates for specific therapy, including enzyme replacement, bone marrow/stem cell transplant, or gene therapy.

Several states have recently expanded newborn screening to identify infants and young children with leukodystrophies; in Pennsylvania, the newborn screening will soon include seven new diseases (Fabry, Krabbe, Pompe, Niemann-Pick, Gaucher, adrenoleukodystrophy, and Hurler syndrome). To support the needs of a greater number of infants identified at birth, and to offer specialized and integrated clinical care for children living with these conditions, Children’s Hospital of Philadelphia recently developed the Leukodystrophy Center of Excellence.

One of only a handful of centers of its kind in the nation, the Leukodystrophy Center brings together a multidisciplinary group of caregivers to provide cutting-edge, comprehensive diagnostic testing, clinical care, and the most advanced treatment to infants and children with inherited white matter disease. CHOP is home to one of the largest pediatric neurology divisions in the world and to the world-class Metabolic Disease Program with the ability to perform the latest genetic sequencing. Children’s Hospital also has expertise in bone marrow and stem cell transplantation, making it the ideal setting for the center.

Four key components of the Leukodystrophy Center

Newborn Diagnostic Clinic

When Pennsylvania and New Jersey implement screening for the additional disorders, the newborn program will provide rapid consultation by metabolic experts and neurologists for infants with a positive screening result. CHOP will perform confirmatory diagnostic testing and a committed genetic counselor and social worker will offer parental counseling. Positive infants will be referred to the Leukodystrophy Center Comprehensive Care Clinic and Therapeutics Program.

Comprehensive Care Clinic

For children already living with the complex challenges of these conditions, we provide state-of-the-art care through a multidisciplinary team incorporating neurology, metabolism, complex care pediatrics, rehabilitation medicine, physical therapy, occupational therapy, speech therapy, and nutrition with additional nursing and social work support. Appointments are scheduled so patients see the whole team in one day and in one location.

Therapeutics Program

The Leukodystrophy Center emphasizes the creation of cutting-edge therapeutic strategies for distinct leukodystrophies as well as care algorithms for monitoring and initiating enzyme replacement, bone marrow or stem cell transplantation, or gene therapy. Currently available treatments are being evaluated for efficacy, and relevant metrics for patient monitoring and patient-centered outcomes will be defined. For each disorder, the team is liaising with other programs worldwide to identify current best practices. Collaborations will be established whenever possible, with a primary goal of evidence-based strategies. The Leukodystrophy Center team is carefully constructing a database and standard operating procedures for laboratory monitoring, imaging and clinical evaluations.

Discovery

A clear imperative exists to advance treatment options for these currently fatal disorders and translate basic discovery to first-in-human trials, and subsequently into collaborative clinical trials. CHOP is ideally suited to achieve this, with the partnerships between the University of Pennsylvania’s Orphan Disease Program, Veterinary School, and with multiple research teams at Children’s Hospital and the University of Pennsylvania. Animal and cell-based models are already actively researched at CHOP and Penn, but this new collaborative will establish regular team meetings, shared concepts, and a clear link with the therapeutics program essential for meaningful translation.

“We are delighted to provide a comprehensive program to meet the medical needs of children with leukodystrophies,” says Amy Waldman, MD, medical director of the Leukodystrophy Center. “We have built an incredible clinical and research team that shares a deep commitment to helping the children afflicted with these illnesses today and to improve therapies for future children.”