Intranasal Foralumab

Alzheimer’s Disease

Emerging evidence suggests that dysregulation of neuroinflammation, particularly that orchestrated by microglia, plays a significant role in the pathogenesis of Alzheimer’s disease (AD). Danger signals including dead neurons, dystrophic axons, phosphorylated tau, and amyloid plaques alter the functional phenotype of microglia from a homeostatic (M0) to a neurodegenerative or disease-associated phenotype, which in turn drives neuroinflammation and promotes disease. Thus, therapies that target microglia activation constitute a unique approach for treating AD. Here, we report that nasally administered anti-CD3 monoclonal antibody in the 3xTg AD mouse model reduced microglial activation and improved cognition independent of amyloid beta deposition. In addition, gene expression analysis demonstrated decreased oxidative stress, increased axogenesis and synaptic organization, and metabolic changes in the hippocampus and cortex of nasal anti-CD3 treated animals. The beneficial effect of nasal anti-CD3 was associated with the accumulation of T cells in the brain where they were in close contact with microglial cells. Taken together, our findings identify nasal anti-CD3 as a unique form of immunotherapy to treat

Alzheimer’s disease independent of amyloid beta targeting.
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques, neurofibrillary tangles, and microglial activation. Therapies targeting amyloid beta have shown positive effects in subjects with AD. Nasal anti-CD3 has been shown to treat animals with a progressive form of experimental autoimmune encephalomyelitis, a model for multiple sclerosis, by inducing regulatory T cells that dampen microglial inflammation in the brain. Here, we show that nasal anti-CD3 also ameliorates disease in a murine model of AD by targeting microglial activation in the brain independent of amyloid beta deposition. These studies identify a unique approach to treat Alzheimer’s disease that could also be given in combination with anti-amyloid therapy.



Preclinical studies suggest possible benefit in preventing and treating Amyloid-related imaging abnormalities (ARIA).
Amyloid refers to beta-amyloid, a protein that forms plaques in the brains of individuals with Alzheimer’s disease. ARIA refers to abnormalities that can be detected through neuroimaging techniques, such as magnetic resonance imaging (MRI) or positron emission tomography (PET). These abnormalities are associated with the accumulation of amyloid in the brain.

There are two main types of ARIA:

ARIA-E (Edema): This type is characterized by the presence of fluid (edema) in the brain, and it is a potential side effect associated with some experimental drugs that target beta-amyloid. ARIA-E is monitored closely in clinical trials, as it may require adjustments to the dosage or discontinuation of the drug.

ARIA-H (Hemorrhage): This type involves the presence of microhemorrhages or small bleeds in the brain. Like ARIA-E, ARIA-H is closely monitored in clinical trials.

These imaging abnormalities are important considerations in the development of drugs aimed at reducing or removing beta-amyloid in the brain as a potential treatment for Alzheimer’s disease. Researchers and clinicians carefully evaluate the occurrence of ARIA to better understand the safety and efficacy of experimental treatments.