Development of gene therapy for neurological disorders.
Given improvements in viral vector design, production and efficiency of transduction in the central nervous system (CNS), as well as increased knowledge of neuropathological mechanisms in neurological disorders, success in treating a CNS disorder with gene transfer seems inevitable. Several different vector systems have been studied extensively and the adeno-associated viral vector system has been utilized in most early stage clinical trials in neurological disorders. Other vector systems, such as lentivirus, adenovirus, and herpes simplex virus are also viable vector platforms that should fill significant clinical niches based on their specific characteristics. In addition to the choice of the appropriate vector, the proper choice of transgene for the appropriate strategy to treat a neurological disorder is also critical. The example of glial cell line-derived neurotrophic factor ligands to treat Parkinson's disease is used to illustrate the importance of the interface between interpretation of pre-clinical data and consideration of the natural history of the disorder. This interface dictates the proper design of clinical trials that are capable of testing whether the treatment is actually successful.
Manfredsson
Fredric P
FP
Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32611, USA. fredric@mbi.ufl.edu
Mandel
Ronald J
RJ
D002986:Clinical Trials as Topic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000627:therapeutic use; D006801:Humans; D010300:Parkinson Disease / Q000628:therapy*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D051098:Glial Cell Line-Derived Neurotrophic Factors