A recent study led by Mass General Brigham researchers found that a nasal spray developed to target inflammation in the brain could be used to treat chronic symptoms of traumatic brain injury.
A nasal spray, referred to as nasal anti-CD3, could be the first FDA-approved treatment for traumatic brain injury, or TBI, that can be easily administered with no serious side effects, the researchers said.
“Most [TBI] treatment is toward symptomatic management of some of the symptoms, but there is no FDA-approved treatment to address the underlying mechanism,” said Saef Izzy, head of the Immunology of Brain Injury Program at the Ann Romney Center for Neurologic Diseases and associate professor of neurology at Harvard University. “We think the outcome of this research will be very impactful.”
Nasal anti-CD3 has previously shown promise for treating other conditions such as Alzheimer’s and multiple sclerosis, according to Howard L. Weiner, co-director at the Ann Romney Center.
“Since I was in training, I’ve been very touched by patients with brain injury and their journey with suffering that happened beyond the injury,” Izzy said in an interview this month. “It goes beyond their discharge, with all the spectrum of PTSD, anxiety, depression, and cognitive decline.”
Following successful trials for treatment of Alzheimer’s, researchers began to study the drug’s ability to treat other brain conditions related to inflammation. In 2020, they set their sights on TBI, which Izzy described as a leading cause of death and health issues across age groups.
The researchers said they hope that nasal anti-CD3 will benefit a variety of patients, from military servicemembers to athletes and crash victims.
“The beauty of it in terms of treating people, is that it doesn’t have any [serious] side effects,” Weiner said. “That’s very, very important. Many drugs have side effects.”
Nasal anti-CD3 can be easily administered at home by family or by the patients themselves, Weiner said. The drug can also be taken in combination with other therapies without complications, the researchers said.
Researchers said they found that the nasal spray could reduce damage to the central nervous system and minimize symptoms associated with brain injury such as memory decline, decreased coordination, and injury-related anxiety.
Chronic inflammation is a key factor in TBI-related health problems, specialists say. The study, published in February in Nature Neuroscience, found that modulating the body’s inflammatory response led to improved TBI symptoms.
The nasal spray works by “expanding regulatory cells which travel to the brain and communicate with other cells assisting in cleaning brain injury-related debris and modulating the inflammatory response over time,” Izzy said.
Injuries can disrupt the blood-brain barrier and cause brain cells to die. As they die, they release chemicals that attract other cells, known as microglia, to stabilize the environment, Izzy said. But microglia cells can play a detrimental role over time, researchers said.
“We have enough evidence in preclinical and clinical trials in mice and humans that these cells remain activated after injury and could be linked to bad outcomes,” Izzy said.
The study was conducted on mice, but Izzy said “we are highly confident that translating this to the human side will lead to beneficial outcomes.”
“Clinical trials are needed,” Izzy said. “That’s what we do in medicine, but we are optimistic about the translation.”
In the study, researchers said they made observations about immune response over time and compared differing immune responses and effects of TBI in mice, accounting for gender.
Researchers at Mass General are now working to translate the preclinical findings to human patients.
Izzy said that the study’s success extends beyond nasal anti-CD3.
“Within five years, we were able to get into the mechanistic aspect of the treatment,” Izzy said. “How cells travel, how they communicate, and how this communication is taking place at what time point... we were able to define it at the cellular and mechanistic level with that, and we’re very excited about about the results.”
Izzy said the findings could translate into treatment of other acute neurological diseases, such as ischemic and hemorrhagic stroke and traumatic spinal cord injury.
After spending extended time in the neurocritical care unit at Brigham and Women’s Hospital and studying long-term outcomes of TBI patients, Izzy said he was inspired to find a potential solution for people with chronic TBI symptoms.
Izzy was the 2024 recipient of the Stepping Strong Breakthrough Award for his work researching TBI treatment and was granted funds to expand his research to traumatic spinal cord injury.
Sarah Mesdjian can be reached at sarah.mesdjian@globe.com. Follow her on X @sarahs_journal.