A drug that blocks the action of a key enzyme could substantially reduce brain damage if administered shortly after a stroke, a new research suggests.
The findings determined in rodent models that aberrant Cdk5 activity causes nerve cell death during stroke.
"If you inhibit Cdk5, then the vast majority of brain tissue stays alive without oxygen for up to one hour," said Dr James Bibb, senior author of the study from the University of Texas Southwestern Medical Centre.
"This result tells us that Cdk5 is a central player in nerve cell death," said Bibb.
More importantly, development of a Cdk5 inhibitor as an acute neuroprotective therapy has the potential to reduce stroke injury.
"If we could block Cdk5 in patients who have just suffered a stroke, we may be able to reduce the number of patients in our hospitals who become disabled or die from stroke. Doing so would have a major impact on health care," Bibb said.
While several pharmaceutical companies worked to develop Cdk5 inhibitors years ago, these efforts were largely abandoned since research indicated blocking Cdk5 long-term could have detrimental effects.
Based on Bibb's research and that of others, Cdk5 has both good and bad effects. When working normally, Cdk5 adds phosphates to other proteins that are important to healthy brain function.
On the flip side, researchers have found that aberrant Cdk5 activity contributes to nerve cell death following brain injury and can lead to cancer.
"Cdk5 regulates communication between nerve cells and is essential for proper brain function. Therefore, blocking Cdk5 long-term may not be beneficial," Bibb said.
"Until now, the connection between Cdk5 and stroke injury was unknown, as was the potential benefit of acute Cdk5 inhibition as a therapy," said Bibb.
In this study, researchers administered a Cdk5 inhibitor directly into dissected brain slices after adult rodents suffered a stroke, in addition to measuring the post-stroke effects in Cdk5 knockout mice.
"We are not yet at a point where this new treatment can be given for stroke. Nevertheless, this research brings us a step closer to developing the right kinds of drugs," Bibb said.
The study was published in the Journal of Neuroscience.
