Gene therapy for dopamine replacement.
Dopamine replacement for Parkinson's disease (PD) have seen three major iterations of improvements since the introduction of l-3,4-dihydroxyphenylalanine (l-DOPA) pharmacotherapy: dopamine receptor agonists, ex vivo gene transfer for cell transplantation and most recently in vivo gene therapy. In this chapter, we describe the principles behind viral vector-mediated enzyme replacement in PD. We focus on the enzymes involved in the dopamine synthesis and their internal regulation, the early experimental work on gene therapy using different viral vector types and selection of transgenes, and finally discuss the recently completed early phase clinical trials in PD patients.
Björklund
Tomas
T
Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, Lund, Sweden. tomas.bjorklund@med.lu.se
Cederfjäll
Erik Ahlm
EA
Kirik
Deniz
D
D000818:Animals; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000627:therapeutic use; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004343:Drug Implants; D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics / Q000628:therapy*; D014780:Viruses / Q000235:genetics
D015259:Dopamine Agents; D004343:Drug Implants; D004295:Dihydroxyphenylalanine; D004298:Dopamine