PROGRAMS - Huntington's Disease

A Synaptic Functional Approach to Huntington's Disease

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the huntingtin gene. A large body of emerging evidence indicates that alterations in synaptic transmission are key underlying factors in multiple neurodegenerative disorders including HD. Several lines of evidence suggest that synaptic transmission is affected in HD prior to the occurrence of neuronal loss and overt motor disturbances. However, the precise synaptic effects of mutant huntingtin have not been defined. We believe that understanding the synaptic biology of HD and other neurodegenerative disorders provides the essential basis for a new, functional therapeutic strategy.

Our synaptic transmission platform provides a unique capacity to comprehensively define synaptic and network alterations induced by mutant huntingtin. Using the MANTRA™ system, we are identifying the specific changes in synaptic function that occur in HD prior to synapse and neuronal loss. With our integrated in vivo EEG and behavioral measures, we are characterizing EEG alterations in the HD brain that emerge prior to overt behavioral and motor symptoms. Our goal is to apply these synaptic and network screening measures to identify a new class of therapeutic candidates that restore synaptic and network activity in HD and to establish a corresponding EEG biomarker to guide clinical development. We believe that therapies with this functional profile will have the potential to be disease modifying and provide symptomatic benefit. We are working closely with CHDI and receiving funding from CHDI to advance our HD discovery program.