Lottery winnings land at KU Medical Center to fund research for a rare genetic disease
A new research grant awarded to the KU Medical Center will support investigation into a neurological condition and has its roots in a Powerball jackpot.
On the same day Paul Rosenau won the $180,100,000 Powerball in Minnesota, he was privately grieving. May 3, 2008, was the fifth anniversary of his 2-year-old granddaughter’s death. At a press conference to announce the largest-ever lottery winner in the state’s history, Rosenau spoke about how Makayla died following her battle with Krabbe’s (pronounced “crab-ay’s”) Disease, a rare, hereditary neurological condition. That same day, Krabbe’s Disease was the most searched topic on Google.
Paul and his wife, Susan (who has since passed away), decided to earmark their jackpot to fight the very disease that took their grandchild too soon. The whole family was tested and learned both Makayla’s parents are carriers for Krabbe’s Disease. Shortly afterward, the Rosenau’s established a foundation — and now 14 years later, they’ve awarded more than $22 million to researchers and supported advocacy in eight state legislatures to establish mandatory testing at birth.
In the latest round of research grants from the Rosenau Family Research Foundation, Steven LeVine, Ph.D., professor of cell biology and physiology in the University of Kansas School of Medicine was awarded $360,000 over three years. His previous research on the disease at KU School of Medicine extends back to 1992.
Steven LeVine, Ph.D.,
professor of cell biology
and physiology, KU
School of Medicine
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’s 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.
“The most common presentation occurs in infants, where it has a rapid disease course resulting in death before 2 or 3 years of age,” LeVine said. “Umbilical cord blood or bone marrow stem cells containing normal levels of the GALC enzyme may be used in infants in an effort to stop progression of the disease. Administering the procedure within the first month of life, before symptoms present, results in a better outcome.”
“We’re very excited to support Dr. LeVine’s research project," said Gabriel Cohn, M.D, MBA, executive director of Rosenau Family Research Foundation. "We found that his proposal was built upon recent scientific findings and thoughtfully proposed an innovative approach to extend these learnings to therapeutics. If successful, his approach could speed the development of a new therapeutic modality for Krabbe’s and significantly improve the lives of those impacted by this condition, as well as helping individuals live life undefined by those diseases.”
Another aspect of the foundation’s mission is to impact state legislation to mandate testing for Krabbe’s Disease at birth, since earlier treatment results in better outcomes. Currently, only 11 states require this testing, including Missouri but not Kansas.
“The bottom line is, this is a devastating disease,” LeVine said, adding, “Our research focuses on improving the quality of life for the patient.”
Learn More
What is Krabbe's Disease?
Krabbe’s Disease (also known as Krabbe Disease) is a rare inherited neurological condition, part of a group of neurological disorders called leukodystrophy — a loss of protective fatty tissues around nerve fibers. Also typical of the disease are abnormal cells in the brain called globoid cells, which are large cells with more than one nucleus.
Krabbe’s is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination) in the nervous system. A myelin sheath is a protective sleeve that is wrapped around each nerve cell and ensures the rapid transmission of nerve signals.
Krabbe’s symptoms include slowed mental and physical development, muscle weakness, blindness, hearing loss and seizures. It is a fatal disorder.
Who does Krabbe’s Disease affect?
Approximately 90% of Krabbe’s Disease cases are diagnosed between 1 and 7 months of age. The late-onset and more rare form of the condition occurs at 18 months or a later age, including adolescence and adulthood.
How common is Krabbe’s Disease?
Researchers estimate that it occurs in 1 per 100,000 live births in Europe and about 1 per 250,000 live births in the United States.