Diane Jaworski, Ph.D.
Dr. Jaworski's laboratory utilizes a wide variety of in vitro and in vivo cellular and molecular biological approaches to investigate the role of extracellular matrix proteolysis in the normal and diseased nervous system, with particular emphasis on gliomagenesis. Our ability to cure glioma is greatly hindered by the fact that at the time of diagnosis tumor cells have invaded to distant sites, making surgical resection palliative rather than curative. Another treatment challenge is recurrence due to the persistence of chemotherapy and radiation resistant glioma stem cells. The hypothesis being tested is that restoration of acetate bioavailability may provide a safe and efficacious means to reduce glioma cell growth. N-acetylaspartate (NAA) is the most concentrated metabolic sources of acetate in the human brain, but the enzyme that cleaves NAA to generate acetate, aspartoacylase (ASPA), is down-regulated in glioma. The lab has demonstrated that the FDA approved food additive Triacetin (glyceryl triacetate, GTA) can bypass ASPA deficiency to serve as an acetate delivery vehicle. Unlike free acetate, GTA can freely cross the blood-brain barrier and enter cells. Pre-clinical studies in the lab have shown that GTA reduces glioma stem cell growth in vitro and enhances chemotherapeutic efficacy to increase survival of murine orthotopically grafted with glioma stem-like cells. GTA has been chronically administered to infants with an ASPA mutation with no significant side effects. An international PCT patent protects develop of GTA as a chemotherapeutic adjuvant. A phase I clinical trial is planned in the near future.