Pharmaceutical Development for Huntington’s Disease

Huntington’s disease (HD) is a devastating neurological disorder caused by mutations in the human gene encoding the huntingtin protein, htt. Since the identification of the HD gene nearly 15 years ago, there has been enormous progress in understanding the molecular features of HD pathology at the cellular level, as well the development of a plethora of HD models in the mouse and other experimental organisms. These studies have led to the beginnings of a systematic process of target selection and validation in the service of formulating rational strategies for pharmaceutical development of HD therapeutics (see Chapter 4, this volume). Some of these targets have matured to the point of being the subjects of directed translational research programs in academia, biotechnology, and pharma organizations. This chapter will describe some of the features that have made the identification of treatments for HD a challenge and how the field is moving forward in the face of such challenges. In particular, we will focus on the activities of the CHDI Foundation, Inc. to bring disease-modifying treatments to the clinic.