Foralumab, CD3 Antibody, Shows Promise in Alzheimer’s Mouse Model
Intranasal treatment works to lower inflammation; Alzheimer's trial possible
Intranasal, or into-the-nose, delivery of foralumab, an investigational antibody-based treatment being developed by Tiziana Life Sciences, restored the activity of microglial cells and improved cognition in a mouse model of Alzheimer’s disease.
Formerly known as NI-0401, foralumab acts to lower inflammation by blocking the activity of CD3, a protein present on immune T-cells. Various formulations of the treatment are also being developed for people with multiple sclerosis (MS), Crohn’s disease, and type 1 diabetes.
Based on the preclinical findings, Tiziana is considering starting clinical trials in Alzheimer’s patients, the company stated in a press release.
“It is an exciting option that could open an entirely new approach for the immunotherapy of neurologic diseases,” said Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the Brigham and Women’s Hospital, chairman of Tiziana’s Scientific Advisory Board, and a study investigator.
“We look forward to evaluating Foralumab clinically in the area of Alzheimer’s disease,” Weiner added.
Weiner discussed the preclinical findings at the recent Alzheimer’s Association International Conference in a presentation titled, “Treatment of Alzheimer’s disease by modulation of microglial neuroinflammation by nasal anti-CD3 mAb.”
Signs of improvement in 2 MS patients given foralumab in EAP
Excessive activation of microglia — the resident immune cells of the brain — has been previously implicated in the progression of neurodegenerative diseases that include Alzheimer’s, Parkinson’s disease, and MS.
In animal models, foralumab has shown an ability to promote the function of regulatory T-cells, a class of immune cells which work to suppress the inflammatory activity of other immune cells.
Two patients with secondary progressive MS treated with foralumab nasal spray under an expanded patient access program (EAP), conducted at the Brigham hospital, showed diminished microglia activity in the brain and signs of neurological improvements were observed. As of June, their treatment was continuing.
Data from the Alzheimer’s mouse model showed that intranasal foralumab similarly led to more normal microglial activity and better cognition.
Genetic profiling of microglia indicated that the cells expressed more genes linked to homeostatic processes, or those that work to restore more normal functioning.
Data also showed that regulatory T-cells traveled into the brain, where they interacted with microglia.
“Nasal anti-CD3 [foralumab] provides a unique approach for treating progressive neurologic diseases by modulating microglial cells,” Weiner said.
“The nasal route of immunotherapy has minimal toxicity and induces regulatory T cells locally, that then migrate to the brain to dampen brain inflammation.”
Cognition was evaluated using the Y-maze and Morris water maze tests, two memory tests often used in mice, and indicated that foralumab led to improvements, Tiziana stated.
“Dr. Weiner has identified another potentially valuable application of anti-CD3,” Matthew Davis, MD, chief scientific officer and chief medical officer of Tiziana, said, adding that Weiner “has conducted extensive work using anti-CD3 in neurological conditions and we look forward to beginning a program in [Alzheimer’s disease] at the appropriate time.”