Gene therapy for Parkinson's disease.
The once fantastic theoretical concept that patients with Parkinson's disease (PD) would receive gene therapy in an attempt to alleviate their symptoms and potentially modify the course of their disease has become a reality. On the basis of positive preclinical data, four different gene therapy approaches are currently in Phase I or Phase II clinical trials. Some approaches are intended to increase levels of endogenous dopamine or enhance the function of the prodrug levodopa. Others are intended to normalize basal ganglia circuitry by reducing the PD-related overactivity of specific brain structures such as the subthalamic nucleus. Each is intended for symptomatic benefit. Finally, gene delivery of trophic factors that not only augment dopaminergic function but are potentially disease modifying has a strong preclinical database and are also in clinical trials. Each of these approaches is discussed in the present review.
Bjorklund
Tomas
T
Brain Repair and Imaging in Neural Systems, Department of Experimental and Medical Science, Lund University, Lund, Sweden.
Kordower
Jeffrey H
JH
D000818:Animals; D017322:Clinical Trials, Phase II as Topic; D004298:Dopamine / Q000008:administration & dosage; D057487:Enzyme Therapy; D004798:Enzymes / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*
D004798:Enzymes; D036341:Intercellular Signaling Peptides and Proteins; D018698:Glutamic Acid; D004298:Dopamine