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
$524,714.00Â - 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, 2004Â - 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.