Discovery, characterization, and therapy of large animal models of human genetic disease.
Key words: Dog, cat, lysosomal storage disease.
Description of Research
In collaboration with others, a series of metabolic diseases caused by deficient enzyme activities are being studied, including mucopolysaccharidoses (MPS) I, VI, and VII (alpha-L-iduronidase, 4-sulfatase, and ß-glucuronidase deficiencies, respectively), alpha mannosidosis (alpha-mannosidase deficiency), I-cell disease (N-acetylglucosamine-1-phosphotransferase), Krabbe disease (galactosylceramidase), and acute intermittent porphyria (PBG-deaminase deficiency). Five of these diseases are lysosomal storage disorders with clinical phenotypes in the animals that are the same as in affected children. Experiments include administering recombinant human alpha-L-iduronidase intravenously to cats with MPS I and gene therapy using retroviral and AAV vectors. The gene therapy experiments are being performed in MPS I cats and dogs, MPS VI cats, and MPS VII dogs using the species-specific cDNAs except feline MPS I. The somatic cell gene therapy experiments include a) intraocular injections of AAV-4-sulfatase vector virus in MPS VI cats, b) neonatal intravenous retrovirus gene therapy in MPS I and VI cats, MPS I dogs, and MPS VII dogs, and c) intramuscular AAV vectors containing the feline 4S cDNA and human SUMF-1 cDNA.
Please see Dr. Haskins.
Thomas O'Malley, Lab Research Specialist
Ping Wang, Lab Reseach Specialist
Ulana Prociuk, Lab Research Specialist
Angie Huff , Lab Reseach Specialist
Patty O'Donnell, Animal Research Specialist
Karyn Cullen, Animal Technician
PRIMARY AREAS OF RESEARCH COMPETENCE
Ellinwood, N.M., Vite, C.H., and Haskins, M.E. Gene therapy for lysosomal storage diseases: The lessons and promise of animal models J. Gene Medicine 6: 481-506, 2004.Mango, RL, Xu L, Sands, MS, Vogler, C, Seiler, G, Schwarz, T, Haskins, ME, Ponder, KP Neonatal retroviral vector-mediated hepatic gene therapy reduces bone, joint, and cartilage disease in mucopolysaccharidosis VII mice and dogs Mol Genet Metab 82: 4-19, 2004.Sleeper, M.M., Fornasari, B., Ellinwood, N.M., Weil, M.A., Melniczek, J., O’Malley, T.M., Sammaroc, C.D., Xu, L., Ponder, K.P., and Haskins, M.E. Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII Circulation : , 2004.Suter, S.E., Gouthro, T.A., McSweeney, P.A., Nash, R.A., Haskins, M.E., Felsburg, P.J., Henthorn, P.S. Isolation and characterization of pediatric canine bone marrow CD34+ cells. Vet. Immunol. and Immunopathology : , 2004.Xu, L., O’Malley, T., Sands, M.S., Wang, B., Meyerrose, T., Haskins, M., Ponder, K.P. In vivo transduction of hematopoietic stem cells after neonatal intravenous injection of an amphotropic retroviral vector in mice Molecular Therapy : , 2004.