Nasal spray shows preclinical promise for treating traumatic brain injury

A new study led by researchers at Mass General Brigham suggests a nasal spray developed to target neuroinflammation could one day be an effective treatment for traumatic brain injury (TBI). By studying the effects of the nasal anti-CD3 in a mouse model of TBI, researchers found the spray could reduce damage to the central nervous system and behavioral deficits, suggesting a potential therapeutic approach for TBI and other acute forms of brain injury. The results are published in Nature Neuroscience.

“Traumatic brain injury is a leading cause of death and disability — including cognitive decline — and chronic inflammation is one of the key reasons,” said lead author Saef Izzy, MD, FNCS, FAAN, a neurologist and head of the Immunology of Brain Injury Program at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. “Currently, there is no treatment to prevent the long-term effects of traumatic brain injury.”

The study examines the monoclonal antibody Foralumab, made by Tiziana, which has been tested in clinical trials for patients with multiple sclerosis, Alzheimer’s disease, and other conditions.

“This opens up a whole new area of research and treatment in traumatic brain injury, something that’s almost impossible to treat,” said senior author Howard Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at BWH. “It also means this could work in intracerebral hemorrhage and other stroke patients with brain injury.”

Multiple experiments were done in mouse models with moderate-to-severe traumatic brain injury to explore the communication between regulatory cells induced by the nasal treatment and the microglial immune cells in the brain. Over time, researchers were able to identify how they modulate immune response.

“Modulating the neuroinflammatory response correlated with improved neurological outcomes, including less anxiety, cognitive decline, and improved motor skills,” Izzy said.

In addition to assessing the effects of the treatment, the research team was able to learn about immune response over time and compare the immune responses and effects of TBI in the mice.

The next step in the research is to translate the findings from preclinical models to human patients.

“Our patients with traumatic brain injury still don’t have an effective therapeutic to improve their outcomes, so this is a very promising and exciting time to move forward with something that’s backed up with solid science and get it to patients’ bedsides,” said Izzy.

Once in the clinical setting, Weiner said the hope is this treatment could be used on a variety of traumatic brain injury patients, including football players with repetitive concussions. 

“We envision giving a nasal spray right there on the sidelines,” said Weiner. “It isn’t something we can do yet, but we see the potential.”

Authorship: In addition to Izzy and Weiner, authors include Taha Yahya, Omar Albastaki, Hadi Abou-El-Hassan, Michael Aronchik, Tian Cao, Marilia Garcia De Oliveira, Kuan-Jung Lu, Thais G. Moreira, Patrick da Silva, Masen L. Boucher, Leah C. Beauchamp, Danielle S. LeServe, Wesley Noguiera Brandao, Ana Carolina Durao, Toby Laser, Federico Montini, Joon-Hyuk Lee, Joshua D. Bernstock, Megha Kaul, Gabriel Pasquarelli-do-Nascimento, Kusha Chopra, Rajesh Krishnan, Rebekah Mannix, Rafael M Rezende, Francisco J. Quintana, and Oleg Butovksy.

Disclosures: Weiner is on the scientific advisory board of Tiziana Life Sciences.

Funding: Izzy reports grants from the National Institute of Neurological Disorders and Stroke (grant no. 5K08NS123503-03), Department of Defense (grant no. HT9425-24-1-0635), 2021 Neurocritical Care Society Research grant and 2023 Stepping Strong Innovator Awards. Izzy and Weiner report a grant from the Department of Defense Multidisciplinary University Research Initiatives Program (grant no. W911NF-23-1-0276). We thank the NeuroTechnology Studio at Brigham and Women’s Hospital for providing instrument (Leica DMi8 Widefield Fluorescence Microscope and Zeiss LSM710 Confocal) access and consultation on data acquisition and data analysis. A Brigham Research Institute Pilot imaging microgrant was received.

Paper cited: Izzy, S., et al. “Nasal anti-CD3 monoclonal antibody ameliorates traumatic brain injury, enhances microglial phagocytosis and reduces neuroinflammation via IL-10-dependent Treg–microglia crosstalk” Nature Neuroscience. DOI: 10.1038/s41593-025-01877-7

Related Information:

Foralumab Nasal Spray May Offer New Hope for MS Treatment | Mass General Brigham

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