BIDMC Scientists Develop Antibody to Treat Traumatic Brain Injury
Bonnie Prescott Beth Israel Deaconess Medical Center staff
SEPTEMBER 01, 2015
Traumatic brain injuries (TBI) affect approximately 20 percent of the more than two million troops who have deployed to Iraq and Afghanistan, and brain injuries caused by repeat concussions affect many professional athletes. TBI is known to be a risk factor for the development of both Alzheimer’s disease and chronic traumatic encephalopathy (CTE), debilitating neurodegenerative diseases for which there is no cure.
Researchers at Beth Israel Deaconess Medical Center (BIDMC) have published a new study in the journal Nature that explains how TBI leads to these two types of dementia, but have also developed a new antibody that can be used to treat traumatic brain injury before it causes widespread brain damage.
“The problem of TBI and concussions developing from repetitive sports injuries among football players and other athletes has gotten a lot of attention in recent years,” explains Dr. Kun Ping Lu, the Director of Translational Therapeutics in the Department of Medicine at BIDMC.
These include the highly publicized case of the late National Football League player Junior Seau, who committed suicide after developing CTE, a degenerative brain disease associated with risk-taking, aggression and depression — and ultimately progressive dementia.
The Tangled Brain
Dr. Lu and co-senior author Dr. Xiao Zhen Zhou have been investigating a brain protein called tau. In healthy brains, the tau protein plays a key role in memory and learning. But in Alzheimer’s and other neurodegenerative diseases, tau can become misshapen and develop into tangles — and subsequent disease.
“We found that the tau protein misfolds and turns into the misshapen cis P-tau, within as little as 12 hours following a traumatic brain injury,” says Dr. Lu. If it is not stopped, the misshapen protein can spread throughout the brain, destroying brain cells and leading to dementia and other serious behavioral and psychological problems.
Dr. Zhou developed an antibody that can intervene to stop this process. Known as a monoclonal antibody, this technology is popular drug development approach that can be used therapeutically to both detect the misshapen protein and then neutralize it so that it goes back to its normal shape.
“This antibody was shown in our animal models to stop the destructive process of cisP-tau,” says Zhou. “The antibody can correct the shape of the protein and turn it back into normal functioning tau.”
This research was conducted in animal models, but the scientists hope that within two to three years, they will be able to develop an antibody therapy that can be tested in humans in clinical trials. And this could conceivably help to treat people after a car accident, military injury or repeated concussions, enabling doctors to identify and treat problems at the very early stages of disease.
"Alzheimer’s disease and chronic traumatic encephalopathy are terrible diseases that progressively rob individuals of their memory, judgment and ability to function,” says Lu. “We will continue to work to develop this antibody in the hopes that one day this clinical treatment will be available to prevent the long-term consequences of TBI in humans.”