New drug-delivery method offers promise in fight against neurodegenerative diseases

by Paul Logothetis, University of Ottawa

edited by Sadie Harley, reviewed by Alexander Pol

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For patients battling neurodegenerative diseases like ALS, Parkinson's, Alzheimer's and other dementias, delivering disease-fighting antibody drugs directly to the brain has proven to be a difficult task. Our bodies set up tight walls to prevent infections from spreading to the brain, where they often become fatal.

Unfortunately, this protective feature also prevents us from getting drugs into the brain. Approximately 1 in 10,000 antibodies injected into patients actually makes it to the brain, with these cellular fighters trapped in the blood rather than escaping through cracks in the blood vessels into the brain.

Now, researchers have mapped out a new transit process to enable drugs to reach the brain using extracellular vesicles—tiny bubbles naturally produced by cells in our bodies.

Researchers at the University of Ottawa showed that extracellular vesicles find a way to squeeze through blood vessels into the brain, allowing them to deliver drugs there. As a next step, they wanted to find ways to improve the ability of antibodies in the brain to eliminate the pathological proteins that cause neurodegenerative diseases.

"Normal antibodies can attach themselves to the disease-causing proteins in these diseases, but they can't eliminate them and so aren't as potent as they could be," explains Dr. Derrick Gibbings, a professor in the Department of Cellular and Molecular Medicine at the University of Ottawa (uOttawa).

Taking out the trash

Autophagy is the body's natural recycling plant, collecting waste from the cell and breaking it up into small pieces that can be reused to build other things useful to cells. Gibbings' team engineered antibodies that attach themselves to disease-causing proteins with a baggage tag that directs these disease-causing proteins into the autophagy garbage disposal system to eliminate whatever the antibodies bind.

"It's a natural cleaning-out process that is normally activated when your cells are stressed or deprived of nutrients. In cells and mouse models, we showed that using autophagy greatly improved elimination of the proteins that cause Alzheimer's, dementia and amyotrophic lateral sclerosis, and mice showed improvements in their symptoms of disease," says Gibbings.

This research, led by Huishan Guo, a research associate in Gibbings' lab, is published in the journal Nature Biomedical Engineering.

Future promise

While this discovery is cause for optimism, Gibbings reminds us this is a first step. Treating mice is one step, but an important one, on the road toward clinical trials and showing benefits in patients.

"There is a lot of enthusiasm for antibodies like these in industry, with many of the major pharma and biotech companies having invested billions of dollars in this space," says Gibbings, a member of the Eric Poulin Center for Neuromuscular Disease.

"Many of these antibodies have been tried in patients in clinical trials but have shown minimal benefits to patients so far. We hope our new strategy to get these antibodies into the brain and eliminate their targets may be a key to making these drugs work for patients."

Publication details

Huishan Guo et al., Engineered autophagy receptors administered with extracellular vesicles eliminate pathological Tau and TDP-43, Nature Biomedical Engineering (2026). DOI: 10.1038/s41551-026-01774-9

Journal information: Nature Biomedical Engineering

Key medical concepts

Extracellular VesiclesAutophagyNeurodegenerative Diseases

Clinical categories

NeurologyClinical pharmacology Provided by University of Ottawa Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Alexander Pol

PhD nano-engineering from Delft University. Published researcher and journal reviewer. Brings scientific insight to content standards. Full profile →

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