title: Gene therapy for dopamine replacement.
abstract: 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.
authors.affiliation: Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, Lund, Sweden. tomas.bjorklund@med.lu.se
authors.forename: Tomas
authors.initials: T
authors.lastname: Björklund
authors.forename: Erik Ahlm
authors.initials: EA
authors.lastname: Cederfjäll
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
mesh_terms: 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
chemical_list: D015259:Dopamine Agents; D004343:Drug Implants; D004295:Dihydroxyphenylalanine; D004298:Dopamine