Researchers have found preclinical evidence that nasal immunotherapy can help reduce inflammation and improve cognition in people with Alzheimer’s disease. 

Alzheimer’s is a debilitating neurodegenerative and neuroinflammatory disease that is difficult to treat. Most existing therapies target the buildup of amyloid beta plaques in the brain, which requires early intervention and intravenous therapy. 

However, in Alzheimer’s experimental models, the new nasal immunotherapy anti-CD3 reduced inflammation and improved cognition independent of amyloid beta plaques.

Incidentally, the therapy is being tested in multiple sclerosis (MS) patients which dampens immune cell inflammation in the brain. 

In the study, published in the journal PNAS, experimental models were treated three times a week with an intranasal anti-CD3 for five months. The therapy effectively limited the activation of microglia immune cells responsible for inflammation in the brain. 

Treated experimental model performed better in behavioural tests, including a water maze, demonstrating improved cognition.

Researchers also identified changes in gene expression patterns in the brain and an expansion of regulatory T cells that fight disease in the periphery following treatment. All changes were independent of amyloid beta plaque levels.

“We provide evidence that intranasal anti-CD3 therapy can dampen microglia activation and expand T cells in an experimental model of Alzheimer’s,” said corresponding author Howard L. Weiner, of the Department of Neurology at Brigham and Women’s Hospital in the US. 

“This represents a unique approach to treating later-stage Alzheimer’s that can be applied to other inflammatory disease conditions as well,” Weiner added.

Researchers plan to investigate the use of this immunotherapy in experimental models in conjunction with anti-amyloid therapies, and expand into human clinical trials.

The work builds upon the team’s previous studies testing foralumab the only fully human anti-CD3 monoclonal antibody treatment in patients with COVID-19 and MS