Waisman Home » Events » Mark Sands, PhD

John D. Wiley Seminar Series

Date: February 10, 2012

Time: Noon to 1:00 pm

Title: "Therapeutic Approaches for Lysosomal Storage Diseases."

Speaker: Mark Sands, PhD
Professor, Department of Medicine, Oncology Division, Stem Cell Biology Section; Department of Genetics
Washington University in St. Louis, School of Medicine

About the Talk: Although the systemic disease associated with lysosomal storage diseases (LSDs) can be effectively treated with intravenous injections of recombinant enzyme, the central nervous system (CNS) disease has been refractory to this approach. Intracranial injection of viral gene transfer vectors has been effective at treating the biochemical, histological, and behavioral abnormalities present in several LSDs. However, several LSDs with profound CNS disease have been resistant to this approach. Therefore, we have developed a combination approach using intracranial delivery of an adeno-associated viral (AAV) gene transfer vector and hematopoietic stem cell (HSC) transplantation. We initially attempted this in the murine model of globoid cell leukodystrophy (GLD) and showed that HSC transplantation synergized with AAV to dramatically improve the behavioral defects and extend the life span. We then determined that the synergy was due, at least in part, to the immunomodulatory effects of HSC transplantation. In order to determine the applicability of this approach to other neurodegenerative LSDs, we performed a similar experiment in the murine model of Infantile Neuronal Ceroid Lipofuscinosis (INCL). INCL is a profoundly neurodegenerative disease. At the terminal stage of disease, the brains of children with INCL are only ~50% the mass of comparably age- and weight-matched children. We also saw dramatic synergy between intracranial AAV and HSC transplantation in this disease. These data are striking in that HSC transplantation was actually deleterious when administered alone but extremely efficacious when combined with AAV. We are currently determining the efficacy of the combination of AAV, HSC transplantation, and a small molecule substrate reduction drug, L-cycloserine, in the murine model of GLD. These approaches have demonstrated unprecedented efficacy in the murine models of disease and will likely form the basis of effective therapies for children with neurodegenerative LDSs.

About the Speaker: I received my B.S in Nuclear Medicine Technology from Rochester Institute of Technology in 1980. I then worked as a Research Technician in the Radiology Department at the University of Rochester Medical Center. In 1984 I entered the Ph.D. program in Pharmacology at Stony Brook University where I received training as a molecular biologist. In 1990 I started my first post-doctoral fellowship at The Jackson Laboratory. There I became interested in lysosomal storage diseases after characterizing the murine model of Mucopolysaccharidosis type VII (MPSVII). I continued to study MPSVII during a 1 year post-doctoral fellowship at the University of Pennsylvania where I also became interested in viral gene transfer vectors. In 1994 I accepted a tenure-track faculty position at Washington University School of Medicine. The goals of my laboratory are to better understand the pathogenesis and develop effective therapies for lysosomal storage diseases. We initially worked with the murine model of MPSVII, however, we have branched out to lysosomal storage diseases that have a more devastating central nervous system component. We have been dissecting the pathogenesis of these diseases by studying the skeletal disease, immune defects, visual deficits, and metabolic abnormalities. We have also developed several effective therapeutic strategies using gene therapy, stem cell transplantation, and small molecule drugs.

Where: John D. Wiley Conference Center, Room T216, Second Floor, North Tower

For Further Information: Contact Teresa Palumbo at 263-5837 or palumbo@waisman.wisc.edu

This Seminar Series is partially funded by the John D. Wiley Conference Center Fund, the Friends of the Waisman Center and NIH grant P30 HD003352.