Scientists were able to determine that anomalous Cdk5 activity is responsible for brain cell death during a stroke in rodents in a study published in the June 11th issue of the Journal of Neuroscience.
“If you inhibit Cdk5, then the vast majority of brain tissue stays alive without oxygen for up to one hour,” said Dr. James Bibb, Associate Professor of Neurology and Neurotherapeutics at UT Southwestern and senior author of the study. “This result tells us that Cdk5 is a central player in nerve cell death.”
Development of a Cdk5 inhibitor as an acute neuroprotective therapy seems to have 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,” Dr. Bibb explained.
Several pharmaceutical companies worked in the development of Cdk5 inhibitors some years ago, this was abandoned because research showed that long-term blocking of Cdk5 could have harmful effects. Scientists believed that anomalous Cdk5 activity was of major importance in developing Alzheimer’s disease and its inhibition might be a beneficial treatment.
The research led by Dr. Bibb has proven that Cd5 has both good and bad effects. This enzyme adds phosphates to other proteins, critical to healthy brain function, when working normally. On the other hand, though, anomalous Cdk5 activity has been found to contribute to nerve cell death following brain injury and it can also cause cancer.
“Cdk5 regulates communication between nerve cells and is essential for proper brain function. Therefore, blocking Cdk5 long-term may not be beneficial,” Dr. 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.”
In performing this study, a Cdk5 inhibitor was administered directly into dissected brain slices, after adult rodents had suffered a stroke. Researchers have also measured 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,” Dr. Bibb said. “We first need to know what mechanisms underlie the disease before targeted treatments can be developed that will be effective. As no Cdk5 blocker exists that works in a pill form, the next step will be to develop a systemic drug that could be used to confirm the study’s results and lead to a clinical trial at later stages.”
The clot-busting drug tPA is currently the only drug approved by FDA for acute treatment of stroke.Other treatment options in order to help minimize brain damage include neurosurgical procedures.