Traumatic brain injuries, whether they occur on a sports field or in a war zone, are on the rise.
What’s worse, these head traumas have been linked to long-term neurodegenerative diseases, notably Alzheimer’s and a condition known as chronic traumatic encephalopathy, or CTE.
Now, a team of researchers report they’ve discovered the “missing link” between traumatic brain injuries and these degenerative brain diseases and developed a special antibody that may help prevent the conditions — at least in mice.
In a study published online in the journal Nature, researchers at Beth Israel Deaconess Medical Center identify the “missing link” culprit as “cis P-tau, a misshapen and toxic species of tau protein that has not been previously identified,” says Kun Ping Lu, MD, PhD, the study’s co-senior author and chief of the Division of Translational Therapeutics in the Department of Medicine at BIDMC and professor of medicine at Harvard Medical School.
Lu, in an interview, explains how these toxic proteins can build up in the brain and start causing serious damage after repeated head injuries:
A single concussion, a mild traumatic brain injury (TBI), results in moderate induction of cis P-tau, which returns to the baseline within 2 weeks. However, repetitive concussions, as might occur in contact sports, result in robust induction of cis P-tau that is persistent for months in mouse brains. This is similar to what is produced following a single severe TBI caused by a blast, as seen in military blast, or an impact, as seen in a severe car accident. Strikingly, cis P-tau is produced as soon as 12 hours after TBI, setting in motion the destructive course of events that leads to Alzheimer’s and CTE.
cis P-tau protein is extremely neurotoxic, disrupting neuron structure and function, progressively spreading to other neurons throughout the brain over time, leading to neuron death. Therefore, cis P-tau has the ability to kill one neuron after another in the brain over time, eventually leading to Alzheimer’s and CTE. These results in animal models are consistent with clinical observations that either repetitive concussions or single severe TBI can lead to Alzheimer’s or CTE.
Importantly, our cis antibody is not only able to spot only the toxic cis P-tau, but also to neutralize its toxicity to neurons. As a result, treating TBI mice with cis antibody can stop brain damage after TBI and prevent its debilitating long-term consequence of Alzheimer’s and CTE. Thus, cis P-tau is an early driver of TBI and its related Alzheimer’s disease and CTE, which can be effectively blocked by antibody therapy.
The immediate implications of these findings are to emphasize TBI prevention; however, if concussion occurs, it is critically important to allow the body defense system to remove the toxic tau protein completely before another concussion occurs. The most exciting development will be to humanize our current monoclonal antibody to develop early intervention to treat TBI and to prevent Alzheimer’s disease and CTE, which can be done within next a few years. In addition, because the same toxic tau protein also destroys brain cells in Alzheimer’s, this early intervention may be used to treat this most common form of dementia in older individuals.
The BIDMC release also states that “Lu and Zhou have interests in Pinteon Therapeutics, Inc., which has licensed Pin 1 technology from BIDMC.” Continue reading