Gene therapy for Parkinson's disease.
Gene therapy is a potentially powerful approach to the treatment of neurological diseases. The discovery of neurotrophic factors inhibiting neurodegenerative processes and neurotransmitter-synthesizing enzymes provides the basis for current gene therapy strategies for Parkinson's disease. Genes can be transferred by viral or nonviral vectors. Of the various possible vectors, recombinant retroviruses are the most efficient for genetic modification of cells in vitro that can thereafter be used for transplantation (ex vivo gene therapy approach). Recently, in vivo gene transfer to the brain has been developed using adenovirus vectors. One of the advantages of recombinant adenovirus is that it can transduce both quiescent and actively dividing cells, thereby allowing both direct in vivo gene transfer and ex vivo gene transfer to neural cells. Probably because the brain is partially protected from the immune system, the expression of adenoviral vectors persists for several months with little inflammation. Novel therapeutic tools, such as vectors for gene therapy have to be evaluated in terms of efficacy and safety for future clinical trials. These vectors still need to be improved to allow long-term and possibly regulatable expression of the transgene.
Horellou
P
P
C 9923 CNRS, Laboratoire de Génétique Moleculaire de la Neurotransmission et des Processus Dégénératifs, Hopital de la Pitié Salpêtriere, Bâtiment CERVI, Paris, France.
Mallet
J
J
D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000637:transplantation; D002470:Cell Survival; D017690:Cell Transplantation; D002478:Cells, Cultured / Q000637:transplantation; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D000229:Dependovirus / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009410:Nerve Degeneration; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000628:therapy; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine