Stem cells offer insights into Huntington's disease

Research on a human stem cell model that encapsulates the pathology of Huntington’s disease (HD) may progress the development of therapeutic interventions for this neurodegenerative disease.

The collaborative proteomics study, conducted by Genea Biocells and Macquarie University, compared the proteins expressed in Huntington’s disease-affected and unaffected human embryonic stem cells (hESCs). Undifferentiated hESCs and hESCs differentiated into neural cells were examined to determine early biochemical changes and pathways involved in disease pathology.

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 HD and people with the condition require full-time care during the later stages of the disease.

The work found that cellular pathways known to be involved in the pathology of HD can be detected in hESCs, providing evidence for the pathology in embryonic stem cells and early neural cell development. In contrast, clinical symptoms appear later in adulthood in most patients with HD patients.

“Analysis of almost 2000 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 Professor Mark Baker said in a statement.

“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.”

The research has been published in the Journal of Proteome Research.