Target: Calpain

Calpain is certainly a little terror after ischemia, and so he's another natural target. Not only could we prevent direct calpain-induced damage, but we could also limit calpain's "cross-talk" to apoptosis and inhibition of protein synthesis. There's even some evidence that calpain indirectly creates free radical species. So by hitting calpain, we could conceivably get at all Four Horsemen. And as it happens, there are calpain inhibitors availabe, such as MDL and leupeptin.

Here's the problem with calpain inhibitors: they don't work. At least, not yet. You can definitely make rats better with calpain inhibitors after stroke or global ischemia, but the improvement is not complete. More to the point, this approach has not, to my knowledge, been tried in humans yet. And as we've already seen, candidate therapies that seem to work in animals often (more like always) fail to cut the mustard in clinical trials.

Figure: Calpain is an attractive target for therapy because he causes so much trouble.