Steven LeVine, Ph.D., professor of cell biology and physiology in the University of Kansas School of Medicine has been awarded $360,000 for a three-year grant from Rosenau Family Research Foundation.
Since the normal development of some brain processes may have been impaired by progression of the disease or the stem cell transplantation procedure, the goal of this new funding is to improve cognitive potential with a new therapy. In an experimental setting using an animal model, LeVine’s research team will test a drug that when used at a low dose may improve the quality of life for young patients.
People with Krabbe Disease have a defect in a gene that results in the impairment of an enzyme known as GALC (galactosylceramidase). GALC is necessary for the production of myelin, a protective layer around nerve cells. GALC also breaks down certain fatty molecules in the brain that are important to the production of myelin. These molecules must be broken down and recycled for the myelin cells to renew themselves and for the brain to remain healthy.
Because people with Krabbe’s Disease have a shortage of GALC, they have a build-up of these molecules in their brains. In 2002, LeVine’s research team demonstrated that substrate reduction therapy, an oral treatment that reduces the production of some fatty molecules, could modestly slow the course of Krabbe’s Disease in mice. And in 2002, they found that combining substrate reduction therapy with hematopoietic stem cell transplantation, also known as a bone marrow transplant, slowed the course of the disease in mice more than did either therapy alone.
With the new funding, LeVine together with Scott Sands, Ph.D., senior scientist in the Department of Dietetics and Nutrition in the KU School of Health Professions, will study whether repurposing an old antibiotic — one that was used to treat drug-resistant tuberculosis — can improve the outcome following stem cell transplantation in experimental conditions. The goal is to improve interventions so that infants and children with Krabbe’s can experience improved quality of life.