Reduction of aggregation in Caenorhabditis elegans models for Huntington’s disease using natural pharmaceutical combinations

Huntington’s disease (HD) is an autosomal dominant disease caused by the destabilization and expansion of the human huntingtin protein (Htt), leading to eventual neurodegeneration. The HD gene is composed of expanded trinucleotide CAG expansions, which can increase in length with age and can impact overall lifespan. Various therapeutic approaches have been evaluated to slow down neurodegeneration, but there are still limited studies of treatment combinations that can be beneficial when combined with one of the leading pharmaceutical treatments, tetrabenazine. In addition, vitamin deficiency has been investigated in the eventual progression of the disease, such as increases in oxidative stress, cell dysfunction, and neural aggregates. Using C. elegans Huntington’s disease models, this study will explore the effects of tetrabenazine (TBZ) supplemented with vitamin B₁ on lifespan, motility, and aggregation. Preliminary lifespan assays of these Huntington’s models have determined an increased survival effect using higher concentrations of vitamin B₁. Using the combinatory supplementation of vitamin B₁ with TBZ, this study aims to explore if aggregate count decreases more effectively through a combinatory vitamin pharmaceutical intervention. This will be assessed by imaging the fluorescent reporters throughout the body wall muscle of transgenic C. elegans analyzed at specific time points throughout their lifespan. This study will also investigate the effects of locomotion and additional metrics, such as area, speed, and wavelength, using tracking assays based on protein aggregation observed at these time points. The effects of lifespan on these C. elegans Huntington’s models will also be explored using the combinations of TBZ treatments using lifespan analysis. The supplementation of vitamins with treatment using these C. elegans models can serve as a potential therapeutic approach in HD by slowing down neurodegeneration, decrease of present symptoms, and the progression of the disease, while providing a cost-effective avenue in finding new therapies.