European Journal of Biomedical and Pharmaceutical Sciences

A REVIEW ON GENE THERAPY FOR HUNTINGTON’S DISEASE

Dr. K. T. Manisenthilkumar*, Shubamalya L. G.

ABSTRACT

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the HTT gene, leading to mutant huntingtin protein aggregation and progressive neuronal loss. Current treatment modalities such as tetrabenazine and supportive measures ameliorate symptoms but are not disease-modifying. Because HD is monogenic, gene therapy has surfaced as an attractive strategy to treat the mutation itself. Herein, we discuss gene silencing methods such as ASOs and RNAi platforms and gene editing platforms indigenously comprising CRISPR/Cas9, zinc finger nucleases, and TALENs. Emphasis is laid upon vectorization systems, which are under extensive investigation looking into safety issues and being able to bypass the blood–brain barrier. Preclinical investigations and early-phase clinical trials (e.g., tominersen, AMT-130) yield positive data with limitations with respect to efficacy and long-term safety. This review discusses the various avenues of gene therapy for HD with a critical emphasis on the potential for disease modification.

Keywords: Huntington’s disease, gene therapy, HTT gene, mutant huntingtin protein, antisense oligonucleotides, RNA interference, CRISPR/Cas9, zinc finger nucleases, TALENs, AAV vectors, lipid nanoparticles, neurodegeneration, disease-modifying therapy, clinical tri