AAIC: Amyloid-Beta Oligomers, an Intranasal Antibody and a Vaccine Targeting Tau

The annual Alzheimer’s Association International Conference (AAIC) is running from July 31-August 4 at the San Diego Convention Center and online. Here are some of the highlights presented so far.

ProMIS’s PMN310 Selectivity on Amyloid-Beta Oligomers

Although many drugs are developed to target amyloid-beta, an abnormal protein associated with Alzheimer’s disease, there are different forms, or oligomers, of the protein. ProMIS Neurosciences presented a poster describing the selectivity of its experimental compound, PMN310, on targeting toxic oligomers.

The company noted that there is evidence suggesting that the most pathogenic form of amyloid-beta in Alzheimer’s is made up of soluble toxic oligomers as compared to insoluble fibrils (plaque) and monomers. In the study, PMN310 demonstrated little or no interaction with monomers and was among the least impacted by excess monomer competition in binding to synthetic oligomers or to naturally occurring toxic oligomers in AD brain extract.

Tiziana’s Intranasal Antibody for Alzheimer’s Disease

Tiziana Life Sciences presented an animal study of its intranasal anti-CD3 monoclonal antibody against Alzheimer’s disease. The preclinical studies demonstrated that activity of microglia - brain-specific immune cells - was restored and cognition improved after receiving the treatment.

The antibody also induced the migration of regulatory T cells (Tregs) to the brain, which then interacted with microglia. Excessive microglial cell activation is associated with a number of neurodegenerative diseases, including multiple sclerosis, Alzheimer’s and Parkinson’s disease.

“Nasal anti-CD3 provides a unique approach for treating progressive neurologic diseases by modulating microglial cells,” Dr. Howard Weiner, M.D., co-director of the Ann Romney Center for Neurologic Diseases at the Brigham and Women’s Hospital (BWH) and chairman of Tiziana’s scientific advisory board said. “The nasal route of immunotherapy has minimal toxicity and induces regulator T cells locally, that then migrate to the brain to dampen brain inflammation. It is an exciting option that could open an entirely new approach for the immunotherapy of neurologic diseases. We look forward to evaluating Foralumab clinically in the area of Alzheimer’s disease.”

Vaxxinity’s Tau Vaccine

Vaxxinity presented new preclinical data on vaccine candidates that target abnormal forms of the Tau protein in Alzheimer’s disease. Like amyloid-beta, tau is a protein that accumulates abnormally in the brains of people with Alzheimer’s disease. Generally, amyloid-beta is observed earlier in the disease and tau later on, although the formation of neurofibrillary tangles (NFT) of tau may develop before the first symptoms of the disease.

“Our findings show that specific forms of Tau can be targeted by vaccines with subsequent functional impact,” Justin Boyd, Ph.D., director of Translational Science at Vaxxinity said. “This preclinical research complements UB-311, our amyloid beta-targeting investigational vaccine which has been granted Fast Track designation by the FDA and it’s in clinical development for Alzheimer’s disease.”

Boyd went on to say, “Vaccines are uniquely suited to deliver multiple antigens in a single formulation, and thus rather than rely on selecting just one epitope, targeting multiple Tau epitopes may provide a more efficient way of neutralizing all toxic Tau species within one program. We look forward to the continued evaluation of these candidates as potential innovative solutions for patients who have been without options for far too long.”