title: Investigational agents for the management of Huntington's disease.
abstract: An inherited, chronic progressive, neurodegenerative disorder is Huntington's disease, characterized by motor, cognitive, and psychiatric symptoms. Predictive genetic testing allows earlier diagnosis and identification of gene carriers for Huntington's disease. These individuals are ideal candidates for testing of therapeutic interventions for disease modification. Areas covered: According to queries in Pubmed, Embase and clinical register databases, research and clinical studies emerge on symptomatic and neuroprotective therapies in Huntington's disease. This review discusses novel agents for symptomatic therapy and disease modification. They are currently in phase I and II of drug development Expert opinion: There are promising, safe and well tolerated compounds for amelioration of motor and neuropsychiatric symptoms, but their efficacy still needs to be proven in clinical trials. Deterioration of mutant huntingtin expression, antiapoptotic or cell death inhibition as disease modifying concepts was efficacious in models of Huntington's disease. However, the risk for clinical trial failures is high not only due to ineffectiveness of the tested agent. Negative study outcomes may also result from design misconceptions, underestimation of the heterogeneity of Huntington's disease, too short study durations and too small study cohorts.
authors.affiliation: a Department of Neurology , St. Joseph Hospital Berlin-Weißensee , Berlin , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D015507:Drugs, Investigational; D000071058:Huntingtin Protein; D018696:Neuroprotective Agents
keywords: Huntington’s disease; disease modification; neuroprotection; study design; symptomatic treatment; tetrabenazine