A research team at the University of Alberta has uncovered a significant new function of brain molecules called gangliosides, which may open avenues for treating genetic neurological disorders such as Huntington’s disease. Their findings, published in the journal Science Advances, highlight the role of gangliosides in the formation and release of extracellular vesicles, which are crucial for cell communication and waste disposal.
Principal investigator Simonetta Sipione, a professor of pharmacology, pointed out the unexpected role these molecules play in disease mechanisms. “This contributes to disease pathogenesis and can be a target for therapeutic intervention,” she stated. Previous research from Sipione’s lab indicated that low levels of gangliosides correlate with Huntington’s symptoms, but the specific role of these molecules was not fully understood until now.
The research team previously demonstrated that restoring a specific ganglioside known as GM1 could reverse Huntington’s symptoms in mice. The Brain Canada Foundation reports that one in every 7,000 Canadians is affected by Huntington’s, a genetic disorder characterized by a range of physical, mental, and emotional symptoms. The disease occurs due to the misfolding and accumulation of mutant huntingtin proteins in brain cells, leading to their malfunction and eventual death.
Sipione explained that reduced levels of gangliosides are not only linked to Huntington’s disease but also to Parkinson’s disease and other hereditary neurodegenerative conditions. “When gangliosides are low, the vesicle-mediated cell communication and clearance system doesn’t function properly,” she noted. This dysfunction allows harmful proteins, such as mutant huntingtin, to accumulate, further driving neurodegeneration.
The team’s ongoing research aims to fully elucidate the mechanisms by which gangliosides protect the brain and explore their potential for clinical use. Sipione is collaborating with a biotech firm to examine options for future clinical trials. Although gangliosides can be synthesized or extracted from the brains of animals, they are currently not approved for therapeutic use in North America.
One challenge facing the therapeutic application of gangliosides is their limited ability to cross the blood-brain barrier when injected into the bloodstream. Sipione emphasized that alternative delivery methods, such as nanoparticles, nasal sprays, or spinal injections, might be necessary to ensure effective brain delivery.
As research advances, the potential of gangliosides in treating neurodegenerative diseases continues to be a promising area of study. The implications of this work could significantly impact the management of conditions like Huntington’s and Parkinson’s, offering hope for new therapeutic strategies.
For more detailed findings, refer to the study by John Monyror et al, titled “Gangliosides modulate the secretion of extracellular vesicles and their misfolded protein cargo,” published in Science Advances in 2025 (DOI: 10.1126/sciadv.ady5212).