A World-Leader in Care

On May 20, 2019, David Wenger, PhD, professor of Neurology and director of Jefferson’s Lysosomal Diseases Testing Laboratory, received the 2019 Sue Rosenau Legacy Award from the Legacy of Angels Foundation. The foundation, which supports research on Krabbe disease, recognized Wenger for his nearly five decades of field-leading work on the disease.

Wenger has spent almost his entire academic career doing research on lysosomal storage disorders, especially Krabbe disease, which is caused by various genetic mutations. These mutations result in defective proteins that usually lead to the accumulation of undegraded compounds. Due to the lack of a specific enzyme, galactocerebrosidase (GALC), patients affected with Krabbe disease have defective myelination, the insulation around nerves. In infants, this can lead to tremors, blindness, mental deficits, and eventually to difficulty moving and eating. Most untreated patients die before two years of age. 

“In my lab, these diseases aren’t rare,” Wenger says. “We diagnose them every week and work with doctors and families to get the diagnosis correct so they can understand what is happening.”

To this end, Wenger rejects any reference to rarity, acknowledging that while lysosomal storage diseases are statistically uncommon, labeling them as “rare” clouds physicians’ thinking and may delay them from obtaining the correct diagnosis. The Wenger laboratory helps to fight back against this stigma by offering diagnostic services to clinicians and families from around the world. Since the 1970s, he and his small team have diagnosed more than 4,800 patients—more than any other lab of its kind in the world.

However, their work goes beyond diagnosis. In 1993, Wenger and his team were the first to purify GALC, the enzyme missing in patients with Krabbe disease, and to clone the GALC gene. Having the sequence of the GALC gene allowed them and others to identify the mutations that cause Krabbe disease and to investigate new therapies to treat patients with this disease. Using safe viruses to carry the coding region of the GALC gene into the cells in the central and peripheral nervous systems that need GALC activity, they hope to improve the lives of affected individuals. It appears that combining this gene therapy approach with the current “standard of care,” namely blood stem cell transplantation, will have the greatest impact on the well-being of the treated patients. 

So far, trials in mice and dogs that are missing GALC activity have been promising, with some affected mice living full lifespans with few, if any, symptoms. The next step is to move the therapy into a clinical trial in humans, a project that Wenger hopes will begin within a year.