Behavioral improvement in MPTP-treated nonhuman primates in the HALLWAY task after transfer of TH cDNA to host astrocytes.
Parkinson's disease is a neurodegenerative disease, resulting from deterioration of the substantia nigra which in turn leads to a decrease of dopamine levels in the striatum. Clinically the syndrome is characterized by motor alterations that are treated by the oral administration of levodopa. However, this treatment typically loses efficacy over time and therefore new treatments that procure a steady long term supplement of dopamine are needed. Here we tested the expression of a tyrosine hydroxilase (TH) transgene in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primates own astrocytes. The transgene, whose expression of TH cDNA was controlled by a glial fibrillary acidic protein (GFAP) promoter, was injected into MPTP treated primate's brains using liposomes as a delivery system. Monkeys were tested before and after MPTP administration, and after gene therapy treatment on the HALLWAY behavioral task. Results showed both transgene expression and significant behavioral improvements in the hallway task after the TH cDNA transfer. The behavioral recovery observed in the primates whose astrocytes expressed rat TH, is a first step that warrant further studies using primate's astrocytes as a good cell lineage to express therapeutic molecules.
Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico City, Mexico.
Aurelio
A
Campos-Romo
Rafael
R
Ojeda-Flores
Pablo
P
Moreno-Briseño
Paula
P
Vergara
José
J
Segovia
José D
JD
Carrillo-Ruiz
Juan
J
Fernandez-Ruiz
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects*; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D017072:Neostriatum / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D015259:Dopamine Agents; D005904:Glial Fibrillary Acidic Protein; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase