A major clinical hurdle is that circulating gangliosides do not cross the blood-brain barrier well, prompting exploration of nanoparticles, nasal routes, or spinal injections for effective brain delivery.

Huntington’s disease affects about 1 in 7,000 Canadians and involves misfolding of mutant huntingtin, leading to neurodegeneration and a wide range of symptoms.

University of Alberta researchers have identified a new role for brain gangliosides in the formation and release of extracellular vesicles, linking these lipids to neuron communication and protection with potential implications for Huntington’s disease and other neurodegenerative conditions.

Earlier work showed low ganglioside levels correlate with disease progression, reinforcing the relevance of ganglioside restoration as a therapeutic strategy.

Delivering gangliosides to the brain faces the blood-brain barrier; researchers are considering delivery methods such as nanoparticles, nasal sprays, or intrathecal (spinal) administration to achieve brain delivery.

The team plans to continue mapping the protective mechanisms of gangliosides and assess clinical potential, including collaboration with a biotech partner to explore future trials.

Next steps focus on delineating how gangliosides protect the brain and translating findings into restorative therapies for neurodegenerative diseases.

Clinically, restoring GM1 ganglioside in mice reversed Huntington’s symptoms, underscoring therapeutic potential while noting ganglioside therapies are not yet approved in North America.

Additional support and collaboration supported by multiple funders and within the university, including contributions from students and colleagues in Flow Cytometry.

Gangliosides, which are half fat, half sugar, are crucial for vesicle-mediated cell communication and waste clearance; low levels are associated with disease progression and impaired clearance of toxic proteins like mutant huntingtin.

The Science Advances study shows that reduced ganglioside levels disrupt vesicle communication and clearance, contributing to progression in Huntington’s, Parkinson’s, and other hereditary neurodegenerative diseases.

The research team acknowledges graduate students and co-authors and notes ongoing collaborations to explore clinical trial possibilities.

Lead investigator Simonetta Sipione emphasizes gangliosides’ role in disease pathogenesis and as potential therapeutic targets, with ongoing work to uncover full mechanisms and delivery methods.

Funding and collaboration came from CIHR, Brain Canada Foundation, NSERC, the Huntington Society of Canada, the Alberta Prion Research Institute, and the Canadian Glycomics Network, with work leveraging the university’s Flow Cytometry Facility.