Huntington’s Disease: current therapies and future directions

Abstract

Huntington’s disease is a neurodegenerative disease that have significantly negative impact to cognitive function. In the worldwide range, approximately 5-10 individuals are affected per 100,000 people. At molecular level, the expanded CAG repeats lead to misfolding and aggregation of the huntington protein, which can interfere with cellular metabolism, including transcription, mitochondrial function, and other important physiological processes. Though scientists already have a well-established theory for the pathology of Huntington’s Disease, no effected cure has been developed due to the heavy genetic base of the disease. Despite the genetic barrier to overcome, many therapies have been created to alleviate the symptoms. In this primer, four main therapies are discussed who reduce the mutant huntington protein amount at post-transcriptional level: Antisense Oligonucleotides, Ethyl-Eicosapentaenoic Acid, autophagy modification, and intrabody based immunotherapy. Within each module, it is described how these therapies can reduce the level of mHTT in molecular level and correct the symptom. Development history is also touched upon briefly and discussion about the current status of each approach is made. Clinical prospective and future direction is included at the end as well.