UTMB

Our research focuses on Canavan Disease and PKU. Canavan Disease is a neuro degenerative disease of the white matter of the brain. A knockout mouse was created here at UTMB and research includes:

Gene Therapy - AAV

Stem Cell Therapy

Acetate supplementation with triacetin

PKU research includes:

Maternal PKU - treatment during pregnancy to prevent birth defects

Treatment of PKU with large neural amino acid LNAA

Treatment of PKU with BH4 (tetrahydrobiopterin)

Enzyme Therapy - phenylalanine hydroxylase enzyme therapy

Researchers

Aryan Namboodiri, Ph.D.

Reuben Matalon, M.D., Ph.D.

P. Arun, Ph.D.

Neil GrunBerg, Ph.D.

C.N.Madhavarao, Ph.D.

Raji Mathew, Ph.D.

John Moffett, Ph.D.

Eric Murphy, Ph.D.

Prasanth Sambhu, M.D.

Louis Elsas, M.D.

Richard Koch, M.D.

Funding

Canavan Disease: Pathogenesis and Treatment, total Direct cost $1,515,000, RO-1. April 2006-2010.

John Sealy Memorial Endowment Fund for Biomedical Research Transfer of Aspartoacylase cDNA to genetically engineered Canavan mouse. R. Matalon, Principal Investigator; Total Direct Funds $70,000.00 - Grant No. 2578-02. January 2002 - 2004.

National Institutes of Health Knock-Out Mouse for Canavan disease. Matalon, Principal Investigator; Total Direct Funds $524,714.00 - Grant No. R01 NS38562-01. April, 1998 - 2003.

Response of Phenylketonuria to Tetrahydrobiopterin (BH4) Principal Investigator, $895,415 FD-R-002600-01. April 2005-2008.

BioMarin Pharmaceutical Inc., Clinical Trial "An Open Label, Single and Multiple Dose Study, To Evaluate the Use of Tetrahydrobiopterin to Screen Patients with Phenylketonuria (PKU) of Hyperphenylalaninemia (HPA) for 6R-BH4 $99,000. March, 2004 - May, 2005.

National Institutes of Health Phenylalanine Hydroxylase Deficiency: Response to BH4 = Principal Investigator $149,000.00 - Grant No. R03 HD 40898. April, 2001 - 2004.

National Institutes of Health Effects of Maternal PKU on Pregnancy Outcome. Principal Investigator - Midwest Region $700,000.00. April, 1996 - 2004.

National Institutes of Health Effects of Maternal PKU on Pregnancy Outcome: Principal Investigator $2,934,427.00. April, 1984 - 1996.

Relevant Publications

Surendran, S., Ezell, E.L., Quast, M.J., Wei, J., Tyring, S., Michals-Matalon, K., Matalon, R. Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. Neurosci Lett. Mar 18, 358(1):29-32, 2004.

Sankar Surendran, Edward L. Ezell, Michael J. Quast, Jingna Wei, Stephen K. Tyring, Kimberlee Michals-Matalon, Reuben Matalon Aspartoacylase deficiency does not affect N-acetylaspartylglutamate level or glutamate carboxypeptidase II activity in the knockout mouse brain. J.Brain Res..05.035, 268-271, 2004.

Sankar Surendran, Gerald A. Campbell, Stephen K. Tyring, and Reuben Matalon: Aspartoacylase gene knockout results in severe vacuolation in the white matter and gray matter of the spinal cord in the mouse. Neurobiology of Disease 18 (2005) 385-389.

Sankar Surendran, Gerald A. Campbell, Stephen K. Tyring, and Reuben Matalon: Aspartoacylase gene knockout results in severe vacuolation in the white matter and gray matter of the spinal cord in the mouse. Neurobiology of Disease 18 (2005) 385-389.

Chikkahur N. Madhavarao, Peethambaran Arur, John R. Moffett, Sylvia Szucs, Sankar Surendran, Reuben Matalon, James Garbern, Diana Hristova, Anne Johnson, Wei Jiang, and M.A. Aryan Namboodiri: Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. PNAS, April 5, 2005, vol.102,no.14, 5221-5226.

Heidi Erlandsen, Angel L. Pey, Alejandra Gamez, Belen Perez, Lourdes R. Desviat, Cristina Aguado, Richard Koch, Reuben Matalon, Charles R. Scriver, Magdalena Ugarte, Aurora Martinez, and Raymond C. Stevens: Correction of kinetic and stability defects in PKU patients with certain phenylalanine hydroxylase mutations. Proc Natl Acad Sci USA. Vol 101:16903-8, Nov, 2004.

Sankar Surendran, Dena Matalon, Stephen K. Tyring, Peter L. Rady, GopalRao V. Velagaleti, Reuben Matalon: Altered expression of myocilin in the brain of a mouse model for Phenylketonuria (PKU). Neuroscience Letters 382 (2005) 323-326.

R. Matalon, S. Surendran, J.D. McDonald, A.O. Okorodudu, S.K. Tyring, K. Michals-Matalon and P.Harris; Abnormal expression of genes associated with development and inflammation in the heart of mouse maternal Phenylketonuria offspring. Int.J.Immunopathol. Pharmacol., vol.18,no.3,557-565 (2005).

Reuben Matalon, Kimberlee Michals-Matalon, Richard Koch, James Grady, Stephen Tyring, Raymond C. Stevens; Response of patients with Phenylketonuria in the US to tetrahydrobiopterin. Molecular Genetics and Metabolism 86(2005) S17-S21.

Nenad Blau, Richard Koch, Reuben Matalon, Raymond C. Stevens; Five years of synergistic scientific effort on Phenylketonuria therapeutic development and molecular understanding. Molecular Genetics and Metabolism 86 (2005) S1.

Reuben Matalon; Working to find alternate pku treatments. PKU News, vol 17, no.3, winter 2006.