Therapeutic strategies in Huntington?s disease

Abstract

The pathophysiology of Huntington’s disease (HD) is not well understood because the mechanisms triggered by mutant Huntingtin to induce selective neuronal death in the striatum and cortex are unknown. Therefore, no effective treatment has been developed for this neurological disorder. A number of new molecules have been patented on the basis of mechanisms involved in the pathogenesis of HD such as excitotoxicity, metabolic impairment or trophic support. Antiglutamate therapy has been considered and the development of new antagonists for NMDA receptors with specificity for the NR2B subunit may reduce the cell death induced by mutant Huntingtin. Neuroprotection can also be achieved with antiapoptotic molecules, including trophic factors or antioxidants that selectively block the intracellular pathways activated in striatal and cortical neurons. Understanding of the mechanisms activated by mutant Huntingtin to induce the selective neuronal death in cortex and striatum is expected to lead to the development of neuroprotective treatments to slow or halt illness progression.