A research team at the University of Alberta has revealed a significant new function for brain molecules known as gangliosides, suggesting potential therapeutic targets for conditions such as Huntington’s disease. The findings, published in the journal Science Advances, indicate that gangliosides play a crucial role in the formation and release of extracellular vesicles, which facilitate cell communication and waste disposal.
Principal investigator Simonetta Sipione, a professor of pharmacology, emphasized the unexpected nature of this discovery. “Our recent study has uncovered a quite unexpected role for these fascinating molecules that are half fat and half sugar,” she stated. This research builds on earlier findings from Sipione’s lab, which linked low levels of gangliosides to symptoms of Huntington’s disease. The team previously demonstrated that restoring a specific ganglioside known as GM1 could reverse Huntington’s symptoms in mouse models.
Huntington’s disease affects approximately one in every 7,000 Canadians, according to the Brain Canada Foundation. The disorder arises from the misfolding of the huntingtin protein, which accumulates in brain cells, leading to their dysfunction and eventual death. Sipione noted that low levels of gangliosides, not only in Huntington’s but also in Parkinson’s disease and other hereditary neurodegenerative conditions, impair the vesicle-mediated communication and clearance system. This dysfunction allows harmful proteins like mutant huntingtin to accumulate, further contributing to neurodegeneration.
Research Directions and Clinical Implications
The team plans to delve deeper into the mechanisms by which gangliosides protect the brain and their potential applications in restorative therapies for neurodegenerative diseases. “We are still working to understand the full picture of how gangliosides protect the brain and how they might be used as restorative therapies in neurodegenerative diseases,” Sipione explained. She is also collaborating with a biotechnology company to investigate the feasibility of future clinical trials.
While gangliosides can be synthesized or extracted from the brains of animals used for meat consumption, they remain unapproved for therapeutic use in North America. One significant challenge is the effectiveness of gangliosides when injected into the bloodstream; very little reaches the brain due to the blood-brain barrier. Sipione mentioned that alternative delivery methods, such as nanoparticles, nasal sprays, or spinal injections, may be necessary to ensure effective brain delivery.
The ongoing research into gangliosides could provide new insights into the treatment of not only Huntington’s disease but a range of neurodegenerative disorders. As scientists continue to unravel the complexities of these brain lipids, the prospect of innovative therapies becomes increasingly tangible.
For comprehensive details, refer to the study by John Monyror et al., “Gangliosides modulate the secretion of extracellular vesicles and their misfolded protein cargo,” published in Science Advances in 2025.
