Defanged tPA May Still Protect the Brain
Tissue plasminogen activator (tPA) may protect against the ravages of stroke through mechanisms separate from its clot-dissolving abilities, a study in the Journal of Neuroscience showed.
Manuel Yepes, MD, of Emory University in Atlanta, and colleagues explored the other functions of the drug in cultured neurons from the cerebral cortex. They showed that even when the drug was modified so it no longer converted plasminogen to plasmin, it protected cultured neurons from the stroke-related loss of oxygen and glucose by activating a pathway that helps cells withstand the insult.
When the researchers gave a form of tPA that did not have clot-busting abilities to mice with an induced stroke, they found that the drug still reduced the infarct size.
The experiments also showed that the protective effect could be achieved at lower doses than given in cases of acute stroke, which could have implications for designing a new therapy that does not carry an increased risk of bleeding.
"The risk of bleeding creates a lot of anxiety, and it has resulted in the regrettable fact that only a small number of stroke patients currently benefit from treatment with tPA," Yepes said in a statement.
I have been on the lookout for drugs that could help us post-CCSVI treatment for long-term MS care with the new perspective of MS as the neurological end-stage of a vascular disease.
In CCSVI, any drug that activates a pathway that helps cells withstand the insult of diminished oxygenation and diminished glucose is of interest. I am not familiar with this form of tPA that does not have clot-busting abilities, since all I know about tPA is that it's used to bust clots, so no idea of the risk profile or possible long-term use of it, but it's at least a new unexplored option that fits the new theory.
“tPA is more than a clot-busting drug, it functions naturally as a neuroprotectant."
http://news.emory.edu/stories/2012/07/s ... index.htmlExposing cultured neurons from the cerebral cortex to tPA protects the neurons from dying after being deprived of oxygen and glucose, the researchers found. tPA appears to induce a set of proteins that helps cells deal with the lack of oxygen and glucose that come from an interruption of blood flow.