Huntington's disease: progress and potential in the field.
While the first description of Huntington's disease was reported over a century ago, no therapy exists that can halt or ameliorate the inexorable disease progression. Tremendous progress, however, has been made in significantly broadening the understanding of pathogenic mechanisms in this neurological disorder that may eventually lead to successful treatment strategies. Huntington's disease is caused by the expansion of a CAG repeat in the huntingtin gene, which results in the expression of a mutant form of the protein that is toxic to neurons. Several mechanisms have been identified in mediating this toxicity, such as protein aggregation, mitochondrial dysfunction, oxidative stress, transcriptional dysregulation, aberrant apoptosis, altered proteosomal function and excitotoxicity. With increasing understanding of each of these pathogenic mechanisms, therapeutic strategies have attempted to target specific aspects of each. There have been many encouraging reports of preclinical efficacy in transgenic Huntington's disease mice, from which a number have been extended to human clinical trials with some success. This review focuses on these studies and the compounds that hold promise for treating human Huntington's disease.
Boston University School of Medicine, Department of Neurology, Boston, Massachusetts, MA 20118, USA.
Edward C
EC
Stack
Robert J
RJ
Ferrante
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000639:trends; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D015507:Drugs, Investigational