Advances in the pharmacological management of Huntington's disease

Drugs. 2010 Mar 26;70(5):561-71. doi: 10.2165/11534430-000000000-00000.

Abstract

There is inevitable physical, cognitive and behavioural decline in Huntington's disease (HD), a dominantly inherited progressive neurological disorder. The hallmark of the disease is chorea, an involuntary brief movement that tends to flow between body regions. HD is diagnosed clinically with genetic confirmation. Predictive testing is available; however, it should be undertaken with caution in patients at risk for the disease but without clinical disease expression. Ongoing observational trials have identified not only early subtle motor signs, but also striatal volume, verbal memory and olfaction as possible early manifestations of clinical disease. Multiple areas of the brain degenerate, with dopamine, glutamate and GABA being the predominant neurotransmitters affected in HD. Although many pharmacotherapies have been evaluated targeting these neurotransmitters, few well conducted trials for symptomatic or neuroprotective interventions have yielded positive results. Tetrabenazine is one of the better studied and more effective agents for reducing chorea, although with a risk of potentially serious adverse effects. Newer antipsychotic agents such as olanzapine and aripiprazole may have adequate efficacy with a more favourable adverse-effect profile than older antipsychotics for treating chorea and psychosis. In this review, the pathogenesis, epidemiology and diagnosis of HD are discussed as background for understanding potential pharmacological treatment options. Potential strategies to delay the progression of HD that have been studied and are planned for the future are summarized. Although there is no current method to change the course of this devastating disease, education and symptomatic therapies are effective tools available to clinicians and the families affected by HD.

Publication types

  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Evidence-Based Medicine
  • Humans
  • Huntington Disease / diagnosis
  • Huntington Disease / drug therapy*
  • Huntington Disease / epidemiology
  • Huntington Disease / pathology
  • Neuroprotective Agents / adverse effects
  • Neuroprotective Agents / therapeutic use*
  • Tetrabenazine / adverse effects
  • Tetrabenazine / therapeutic use*
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Neuroprotective Agents
  • Tetrabenazine