Recent advances in Huntington's disease: implications for experimental therapeutics

In this article we have set out to critically review recent advances in the basic and clinical understanding of Huntington's disease, with specific emphasis on those findings that are most relevant to the planning, design, and conduct of future clinical trials for this devastating disorder.

The exact mechanisms underlying neuronal death in Huntington's disease remain unknown. Over the past 10 years, the leading models of neurodegeneration in the disease have involved mitochondrial dysfunction and subsequent excitotoxic injury, oxidative stress, and apoptosis. Recent studies have lent support to these models, but additional theories involving abnormalities of protein metabolism and transcriptional dysregulation have emerged as well. As progress is made toward clarifying the pathophysiological mechanisms leading to Huntington's disease, and new therapies are proposed, investigators have begun to develop improved outcome measures for potential use in future clinical trials aimed at slowing the progression of the disorder.

Recent advances in the understanding of the molecular biology and pathophysiology of Huntington's disease have suggested new therapeutic strategies aimed at slowing progression or forestalling onset of this neurodegenerative disease. In preparation for future clinical trials, clinical studies have begun to provide more quantitative measures of disease onset and progression. This progress in both the basic science and clinical realms raises real hope for effective therapies in the near future.