A family of nanoparticles — tiny, biodegradable molecules commonly used to deliver drugs to patients — shows promise in treating Alzheimer’s disease without additional medication, according to new research from a University of Alberta neuroscientist.
In a study published in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association, Dr. Satyabrata Kar and colleagues report finding improved symptoms and reversal of the disease at the molecular and cellular level in mice with Alzheimer’s following treatment with a class of nanoparticles called polylactic-co-glycolic acid, or PLGA. The nanoparticles have been approved for drug delivery in humans in the United States, Europe and Canada.
“These molecules have a long-standing safety record and are biodegradable,” says Kar, a professor in the Department of Medicine.
“There is really no effective treatment available for Alzheimer’s right now,” he says. “Most treatments are for symptoms only; they do not stop or halt the progression of the disease. And two recently approved disease-modifying treatments have been reported to have severe side-effects in some patients.”
About 750,000 Canadians live with Alzheimer’s disease or another form of dementia, according to Statistics Canada. Alzheimer’s is the most common form of dementia and is the ninth leading cause of death in Canada.
PLGA nanoparticles were first used as biodegradable sutures and were subsequently approved as vehicles for drug delivery in the 1980s. More than 20 drugs are now delivered using PLGA nanoparticles, which can be modified to target certain organs or parts of the body to reduce side-effects.
Kar started working with PLGA nanoparticles in 2020 and has published previous studies showing they protect neurons against toxicity and prevent the aggregations of neuronal proteins associated with Alzheimer's disease.
The latest paper shows that PLGA nanoparticles delivered directly to the brains of animals with Alzheimer’s prevented the overproduction and buildup of beta-amyloid peptides, which lead to dangerous plaques in the brains of Alzheimer’s patients. The researchers also saw improvements in the cognitive and memory functions of the animals following PLGA treatment.
Kar plans further testing of these nanoparticles to validate his results. He is currently collaborating with other researchers to examine how these nanoparticles cross the blood-brain barrier and to increase their half-life so they remain effective longer. Another collaboration is looking at how labelled PLGA nanoparticles can bind to brain plaques, allowing for faster diagnosis of the disease.
Kar is unsure exactly why the nanoparticles have such a pronounced effect in Alzheimer’s, but notes they have impacts on several disease-causing factors. He also says another lab in the United States has recently reproduced some of his results, a sign of further interest in their potential.
“Currently, I am trying to get resources to expedite this project to help patients,” Kar says. "I've been working on Alzheimer's for 30 years and I've never been so excited.”
This research was funded by the Canadian Institutes for Health Research and the Alzheimer Society of Alberta and Northwest Territories, and by a grant from the National Institute on Aging to Kar’s collaborator at the University of South Florida.
Satyabrata Kar is a member of the Neuroscience and Mental Health Institute and the Centre for Prions and Protein Folding Diseases.
