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| Convection-enhanced delivery of AAV vector in parkinsonian monkeys; In vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach |
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| Author(s): Bankiewicz KS, Eberling JL, Kohutnicka M, Jagust W, Pivirotto P, Bringas J, Cunningham J, Budinger TF, Harvey-White J |
| Source: EXPERIMENTAL NEUROLOGY Volume: 164 Issue: 1 Pages: 2-14 Published: JUL 2000 |
| Times Cited: 145 References: 39 |
| Abstract: Using an approach that combines gene therapy with aromatic L-amino acid decarboxylase (AADC) gene and a pro-drug (L-dopa), dopamine, the neurotransmitter involved in Parkinson's disease, can be synthesized and regulated. Striatal neurons infected with the AADC gene by an adeno-associated viral vector can convert peripheral L-dopa to dopamine and may therefore provide a buffer for unmetabolized L-dopa, This approach to treating Parkinson's disease may reduce the need for L-dopa/carbidopa, thus providing a better clinical response with fewer side effects. In addition, the imbalance in dopamine production between the nigrostriatal and mesolimbic dopaminergic systems can be corrected by using AADC gene delivery to the striatum, We have also demonstrated that a fundamental obstacle in the gene therapy approach to the central nervous system, i.e., the ability to deliver viral vectors in sufficient quantities to the whole brain, can be overcome by using convection-enhanced delivery, Finally, this study demonstrates that positron emission tomography and the AADC tracer, 6-[F-18]fluoro-L-m-tyrosine, can be used to monitor gene therapy in vine, Our therapeutic approach has the potential to restore dopamine production, even late in the disease process, at levels that can be maintained during continued nigrostriatal degeneration. (C) 2000 Academic Press. |
| Document Type: Proceedings Paper |
| Language: English |
| Reprint Address: Bankiewicz, KS (reprint author), NINDS, Mol Therapeut Sect, LMMN, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA |
Addresses:
1. NINDS, Mol Therapeut Sect, LMMN, Bethesda, MD 20892 USA
2. Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, Berkeley, CA 94720 USA
3. Avigen Inc, Alameda, CA USA
4. Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA
5. Med Acad Warsaw, Dept Expt & Clin Pharmacol, Warsaw, Poland |
| Publisher: ACADEMIC PRESS INC, 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA |
| Subject Category: Neurosciences |
| IDS Number: 336XM |
| ISSN: 0014-4886 |
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