Douglas R. Martin, PhD

Molecular therapy of neurodegenerative diseases.

Lysosomal storage diseases comprise a group of over forty related disorders that result from dysfunction of lysosomal enzymes or associated proteins. With a frequency of 1 in 7700 live births, these inherited diseases often occur in early childhood and most are currently untreatable. Dr. Martin studies therapeutic strategies for the neuropathic lysosomal storage diseases known as GM1 and GM2 gangliosidosis in well-characterized feline models. Although many types of molecular therapy are being considered, the laboratory focuses primarily on adult stem cell and/or gene therapy with lentiviral or adeno-associated viral vectors. Because normal or genetically engineered donor cells can transfer lysosomal enzymes to diseased cells through a process known as "cross-correction," stem cells are being evaluated as enzyme delivery vehicles. In a more direct approach, replication-defective viruses engineered to express a therapeutic lysosomal enzyme are used to restore enzymatic activity. Dr. Martin and collaborators expect that positive results in the feline model will lead to human clinical trials for these devastating diseases.

Original Research

Bradbury AM, Morrison NE, Hwang M, Cox NR, Baker HJ and Martin DR. Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency. Mol Genet Metab 97:53-59, 2009.

Wang L, Shi J, van Ginkel FW, Lan L, Niemeyer G, Martin DR, Snyder EY and Cox NR. Neural stem/progenitor cells modulate immune responses by suppressing T lymphocytes with nitric oxide and prostaglandin E2. Exp Neurol 216(1):177-83, 2009.

Baek RC, Martin DR, Cox NR and Seyfried TN. Comparative analysis of brain lipids in mice, cats, and humans with Sandhoff disease. Lipids 44:197-205, 2008.

Vig K, Herzog R, Martin D, Moore EG, Dennis VA, Pillai S and Singh SR. Recombinant adeno-associated virus as vaccine delivery vehicles. Gene Ther Mol Biol 12:277-292, 2008. [Review Article]

Martin DR, Rigat BA, Foureman P, Varadarajan GS, Hwang M, Krum BK, Smith BF, Callahan JW, Mahuran DJ and Baker HJ. Molecular consequences of the pathogenic mutation in feline GM1 gangliosidosis. Molec Genet Metab 94:212-221, 2008.

Samoylova TI, Martin DR, Morrison NE, Hwang M, Cochran A, Samoylov A, Baker HJ, Cox NR. Generation and characterization of recombinant feline β-galactosidase for preclinical enzyme replacement therapy studies in GM1 gangliosidosis. Metab Brain Dis 23(2):161-73, 2008.

Wang L, Martin DR, Baker HJ, Gentry AS, Zinn KR, Kappes JC Snyder EY and Cox NR. Neural progenitor cell transplantation and imaging in a large animal model. Neurosci Res 59: 327-340, 2007.

Martin DR, Cox NR, Morrison NE, Kennamer DM, Peck SL, Dodson AN, Gentry AS, Griffin B, Rolsma MD and Baker HJ. Mutation of the GM2 activator protein in a feline model of GM2 gangliosidosis. Acta Neuropathol 110(5):443-50, 2005.

Martin DR, Krum BK, Varadarajan GS, Hathcock TL, Smith BF and Baker HJ. An Inversion of 25 Base Pairs Causes Feline GM2 Gangliosidosis Variant 0. Exp Neurol 187:30-37, 2004.

Martin DR, Cox NR, Hathcock TL, Niemeyer GP and Baker HJ. Isolation and characterization of multipotential mesenchymal stem cells from feline bone marrow. Exp Hematol 30:879-86, 2002.