UB scientists studying Krabbe’s disease take a novel approach to this fatal disease that strikes newborns

BUFFALO, N.Y. — Rep. Brian Higgins visited the New York State Center of Excellence in Bioinformatics and Life Sciences on Monday to announce more than $2 million in National Institutes of Health funding to the Hunter James Kelly Research Institute.

The funding allows UB researchers at the institute to pursue a new approach to Krabbe’s disease, also called globoid cell leukodystrophy, a rare, neurological disease that afflicts newborns and is fatal.

The new approach focuses on the peripheral nervous system as a possible “window” into the disease, according to M. Laura Feltri, MD, and Lawrence Wrabetz, MD, co-directors of the Hunter James Kelly Research Institute and co-principal investigators on the new grant. They are professors in the departments of Biochemistry and Neurology in the Jacobs School of Medicine and Biomedical Sciences at UB.

“What’s exciting about this grant is that we are leading research on Krabbe’s in a new direction,” Feltri said. “Our research will pinpoint which cells need correction, using methods such as gene therapy, in order to cure the disease.”

This new direction, Higgins noted, comes about as a result of the continued investment in the institute, one of a handful of research institutes in the world with an exclusive focus on myelin and diseases of myelin, such as multiple sclerosis, demyelinating neuropathies and leukodystrophies, and how they may be treated.

The institute, part of UB’s New York State Center of Excellence in Bioinformatics and Life Sciences, was established by Buffalo Bills Hall of Fame quarterback Jim Kelly and his wife, Jill, after their infant son, Hunter, was diagnosed with Krabbe’s Disease. He died in 2005 at the age of eight.

Since Feltri and Wrabetz were recruited to UB in 2011 from the San Raffaele Scientific Institute in Milan, the institute has had more than $16 million in research funding. It now employs more than 40 people.

Genetic mutation

Krabbe’s disease is caused by a mutation in the GALC gene, which contains instructions for the synthesis of an enzyme called galactosylceramidase. This enzyme is responsible for breaking down certain fats that accumulate in cells during the production of myelin, the fatty insulator that allows nerve cells to communicate. Without this enzyme, those fats accumulate, ultimately damaging and destroying the nervous system. The result is a severe and ultimately fatal neurological condition in which the child loses the ability to move, chew, swallow, and breathe; they also experience vision loss and seizures. 

Currently, the only treatment for children with Krabbe’s disease is a bone marrow transplant. Feltri explained that the premise has been that through this procedure the patient will be able to take up the healthy enzyme from the donor cells, allowing for normal stability of myelin.

“Based on our preliminary data, we have evidence that this transfer of enzyme to sick cells is inefficient or does not occur at all,” she said. “Rather, the improvement in symptoms that is seen after a bone marrow transplant may result instead from an anti-inflammatory effect and not because of this transfer.”

Using a new animal model of the disease, the UB researchers expect to be able to determine which cells in the peripheral nervous system are involved in Krabbe’s disease and by which mechanism.

Turning point

“We are at an important turning point in our understanding of the mechanisms that contribute to this disease,” Feltri said. “Based on the research done here at the institute, we are finding that we need to rethink some of the previously accepted premises about Krabbe’s disease. This grant will allow us to continue that important work in order to ultimately develop the best therapies to treat and ultimately cure it.”

“Together with progress made at other institutions around the world to determine how to deliver the missing enzyme to the appropriate cells via gene therapy, this will bring us closer to a successful treatment for Krabbe’s disease and similar disorders.”

Researchers at the HJKRI have also received additional NIH funding for Krabbe disease:  more than $800,000 to study “Selective galactosylceramidase ablation to study the pathogenesis of Krabbe leukodystrophy” to Daesung Shin, PhD, research assistant professor of biochemistry in the Jacobs School at UB, as well as a fellowship grant to Nadav Weinstock a doctoral student involved in the research. In addition, Thomas Langan, MD, associate professor of neurology in the Jacobs School, has NIH funding to study how to enhance newborn screening for Krabbe’s disease and Wrabetz has received funding from the European Leukodystrohy Association.