title: Experimental surgical therapies for Huntington's disease.
abstract: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by abnormal movement, cognitive decline, and psychiatric disturbance. HD is caused by a trinucleotide repeat expansion in the HTT gene and a corresponding neurotoxic polyglutamine expansion in the huntingtin protein. There is currently no therapy to modify the progressive course of the disease, and symptomatic treatment options are limited. In this review we describe a diverse set of emerging experimental therapeutic strategies for HD: deep brain stimulation; delivery of neurotrophic factors; cell transplantation; HTT gene silencing using RNA interference or antisense oligonucleotides; and delivery of intrabodies. The common feature of these experimental therapies is that they all require a neurosurgical intervention, either for implantation of an electrode or for brain delivery of molecules, viruses or cells that do not cross the blood-brain barrier upon oral or intravenous administration. We summarize available data on the rationale, safety, efficacy, and intrinsic limitations of each of these approaches, focusing mainly on studies in HD patients and genetic animal models of HD. Although each of these strategies holds significant promise, their efficacy remains to be proven in HD patients.
authors.affiliation: Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Jelle
authors.initials: J
authors.lastname: Demeestere
authors.forename: Wim
authors.initials: W
authors.lastname: Vandenberghe
mesh_terms: D017690:Cell Transplantation; D046690:Deep Brain Stimulation; D016332:Fetal Tissue Transplantation; D020868:Gene Silencing; D015316:Genetic Therapy; D005917:Globus Pallidus / Q000601:surgery; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy / Q000601:surgery* / Q000628:therapy; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000637:transplantation; D019635:Neurosurgical Procedures; D009687:Nuclear Proteins / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D034622:RNA Interference; D033581:Stem Cell Transplantation
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D007128:Immunoglobulin Fragments; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense