[Huntington's disease].

BACKGROUND

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by hyperkinetic movements, psychiatric (e.g. depression and psychosis) and cognitive symptoms (frontal lobe dementia). In Germany approximately 8000 patients suffer from HD.

OBJECTIVES

The paper reviews the clinical course, epidemiology, genetics, differential diagnoses, pathophysiology, symptomatics and causal treatment options.

METHODS

Publications on animal and human HD studies and trials and reviews available in Medline have been taken into account.

RESULTS

Only genetic testing allows diagnostic certainty. The CAG repeat length influences age of onset, disease course and life expectancy. The mechanism by which mutant huntingtin protein (mHTT) causes HD is complex and poorly understood but leads to cell death, in particular in striatal neurons. In clinical trials antioxidants (e.g. coenzyme Q10), selisistat, PBT2, cysteamine, N-methyl-D-aspartate (NMDA)-receptor antagonists and tyrosine kinase B receptor agonists have been studied in HD.

CONCLUSION

No disease-modifying therapy is currently available for HD; however, gene silencing, e.g. through RNA interference, is a promising technique which could lead to effective therapies in due course.