Research conducted by Genea Biocells and Macquarie University describes a human stem cell model that recapitulates Huntington’s disease pathology and offers insights into the cause and progress of the disease.
The findings suggest that stem cells could assist the development of therapeutic interventions for Huntington’s disease (HD).
The joint research, published in the latest edition of the Journal of Proteome Research, compared the proteins expressed in Huntington’s disease-affected and unaffected human embryonic stem cells (hESC), both in the undifferentiated state and differentiated to neural cells to examine the earliest biochemical changes and pathways involved in disease pathology.
“The proteomics study comparing Huntington’s disease-affected and unaffected stem cells and neurons confirms cellular pathways known to be involved in HD pathology. Interestingly, our study shows that those disturbances can be detected even in embryonic stem cells and their early neural development while most HD patients only show overt clinical symptoms later in adulthood,” Genea Biocells General Manager Dr Uli Schmidt said.
“Analysis of almost 2,000 proteins revealed mitochondria as the primary dysfunctional organ in HD-affected pluripotent stem cells, suggesting that energy metabolism and response to oxidative stress is seriously impaired in HD affected cells,” Macquarie University’s Prof Mark Baker said about the published study.
“Furthermore, on the basis of analysis of over 600 proteins, we showed a shift to transcriptional dysregulation and cytoskeletal abnormalities as the primary pathologies in HD-affected cells differentiating along neural lineages in vitro.”
Dr Schmidt added that the contribution of Macquarie University’s Australian Proteome Analysis Facility was essential to the completion of the research.
“Access to Macquarie University’s leading national proteomics provider the Australian Proteome Analysis Facility provided Genea Biocells with essential information for the research and the resulting paper,” he said.
Huntington’s disease is a neurodegenerative genetic disorder that impacts muscle coordination and leads to cognitive decline in sufferers. It affects approximately 5-7 people in every 100,000 in Western countries. There is no cure for Huntington’s disease and people with the condition require full time care during the later stages. Life expectancy is reduced to approximately 20 years from the point at which symptoms become evident.