Open AccessExperimental Surgical Therapies for Huntington's Disease
Author(s) -
Demeestere Jelle,
Vandenberghe Wim
Publication year - 2011
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2010.00209.x
Subject(s) - huntington's disease , deep brain stimulation , huntingtin , disease , medicine , neurotrophic factors , genetic enhancement , neuroscience , huntingtin protein , trinucleotide repeat expansion , gene silencing , transplantation , bioinformatics , psychology , biology , parkinson's disease , gene , genetics , allele , receptor
SUMMARY 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.