The mechanisms surrounding HD are raising interesting viewpoints, especially with the help of R6/2 mice as models, transfected with an adenovirus for the trinucleotide repeat (24). The better we can create novel approaches in tracking the progression of this disease, the better position we will be in to create biomarkers of this disease progression, and be able to identify their resultant manipulation from targeted protein interactions.

By virtue of investigating more into complex pathways within the neurons, such as the Kyuridine Monooxygenase Pathway (KMO), we can come up with novel and targeted practices to understand immune reactions involving mutant htt (mhtt), cytotoxicity, membrane protection, in the ultimate goal of delaying, ceasing, or ameliorating the effects of mhtt.

Various approaches have been made in the attempt to achieve a better understanding of how the mutant huntingtin gene contributes to neural degeneration.  There have been three main approaches in attempting to understand this disease; the immune approach, the protein interaction approach, and virtue of biomarkers and clinical endpoints.

Left: Mutant Htt activates NF-Kappa B-dependent gene expression. (Khoshan et al. 2004.)

Photo: Brain atrophy progresses with onset of HD, where increased atrophy correlates with increased clinical symptoms. (Credit: Ruocco et al. 2008.)

Clinical endpoints are the most credible characteristics used to interpret the results of randomized clinical trials and reflect how a patient feels, functions, or survives, yet limited by virtue of self-objective assessments (29). The need to establish guidelines is essential to gauge the progress of future therapeutic interventions.