The best treatment for a hard knock on the head might someday involve a quick sniff of a nasal spray. Researchers have found early evidence in mice that an antibody-based treatment delivered up the nose can reduce the brain damage caused by concussions and more serious traumatic injuries.
Scientists at Mass General Brigham conducted the study, published Thursday in Nature Neuroscience. In brain-injured mice, the experimental spray appeared to improve the brain’s natural acute healing process while also reducing damaging inflammation later on. The findings could lead to a genuine prophylactic against the long-term impacts of traumatic brain injuries and other conditions like stroke, the researchers say.
Traumatic brain injuries, or TBIs, are a persistent public health problem. According to the Centers for Disease Control and Prevention, over 200,000 Americans were hospitalized by a TBI in 2020, while nearly 70,000 died as a result. Scientists are also learning that TBIs, including the mild ones that we call concussions, can cause lingering neurological issues and may even raise the risk of dementia decades later.
While there are ways to reduce the acute harm caused by TBIs, such as plenty of rest for concussions or surgery for serious injuries, there’s no established medication for preventing the chronic effects of it (that said, brain rehabilitation therapy is often an important part of recovery). In recent years, however, Mass General Brigham researchers have been studying an experimental lab-made antibody called foralumab that’s shown promise for neurological conditions like multiple sclerosis. So they decided to see whether foralumab might also be useful for TBIs.
Foralumab, developed by the company Tiziana Life Sciences, targets a specific group of proteins that interact with the brain’s immune cells, called CD3. This suppression of CD3, the team’s earlier work has suggested, increases the activity of certain immune cells known as regulatory T cells (Treg). As the name implies, these cells help regulate the brain’s immune response to make sure it doesn’t go haywire.
“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 researcher Saef Izzy, head of the Immunology of Brain Injury Program at Brigham and Women’s Hospital, in a statement from Mass General.
In their latest mice study, the researchers found that foralumab—via the increased activity of Treg cells—improved aspects of the brain’s immediate healing from a traumatic injury. The dosed mice’s microglia (the brain’s unique first line of immune defense) became better at eating and cleaning up after damaged cells, for instance. Afterward, the drug also appeared to prevent microglia from becoming chronically inflamed, As a result, relative to mice in a control group, mice treated with foralumab up to three days post-injury experienced greater improvements in their motor function and coordination.
“These findings suggest that nasal anti-CD3 represents a promising new therapeutic approach for treating TBI and potentially other forms of acute brain injury,” the researchers wrote.
Studies in mice and other animals are only the first step in proving that a new drug or vaccine can work as hoped. Quite obviously, more research is needed to validate the drug’s potential for TBI treatment. But foralumab has already shown early positive results in human trials for MS, with other trials for Alzheimer’s and amyotrophic lateral sclerosis having started or soon to be underway. That raises hope that this antibody can become a new and much needed treatment option for numerous brain conditions, TBI included.
