Metabolic Diseases

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

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.