Group of cells expressing mutant huntingtin (in red) in vitro. Yellow puncta are aggregates of mutant huntingtin and p62, a protein involved in the clearance of protein aggregates.
Huntington disease (HD) is an inherited disorder that causes progressive malfunctioning and death of parts of the brain that control movement, reasoning and emotions. HD patients also suffer from depression and personality changes. Symptoms progress steadily until patients can no longer lead a normal life and eventually die. There is no cure for HD. To date, while treatments for symptom control are available, there are no therapies that delay or stop disease progression. Disease-modifying therapies are urgently needed.
The cause of HD is known - people with HD have a mutated protein called huntingtin which becomes toxic. One of the reasons why mutated huntingtin is toxic is that it causes the brain to produce insufficient amounts of a molecule called GM1 (a type of ganglioside) that is important for healthy brain function. Supplementation of GM1 to mouse models of HD dramatically improves the symptoms of the disease and slows down the underlying neurodegenerative process. This suggests that GM1 could be a potential treatment for HD. Previous research by Simonetta Sipione has shown that administration of GM1 to animal models of HD improves symptoms and slows down neurodegeneration, but the underlying mechanisms are still unclear.
In this project, Dr. Sipione and her team will continue their work on gan gliosides, advancing their knowledge towards a potential treatment for Huntington’s disease. Their objective is to identify the mechanisms of action of therapeutically administered gangliosides and also to measure gangliosides in human samples and determine their potential role as biomarkers of HD progression. Altogether, this work will significantly advance the understanding of the mechanisms of action of GM1 in HD and will accelerate the development of ganglioside-based therapies for HD.
The multidisciplinary team assembled for this project includes three biomedical scientists and three clinicians from Alberta and Quebec with experience in the neurobiology of HD, clinical neurology, ganglioside and lipid biology and biochemistry and quantitative proteomics. HD patients and their families are crucial partners in this project as volunteering participants who will provide samples and data for both objectives. This exciting research will pave the way towards a clinical trial in HD patients.
“ We think that our research will have important implications not only for HD but also for other brain diseases where gangliosides have been involved, including Parkinson’s disease. ”
— Simonetta Sipione, Ph.D. Associate Professor, University of Alberta