GvHD causes the cell death of intestinal stem cells. And we investigated a protein that’s called receptor interactive protein one, RIP1, which is involved in cell death. This protein, when is activated, it causes both apoptosis and necroptosis in the intestinal stem cells.
And we study an in vivo model as well as an in-vitro model where we inhibit this protein. And we saw that in the in vivo model this increased survival and alleviates the inflammation in the mouse and also in our in vitro model in intestinal organoids this the inhibition of RIP1 rescues organoids from apoptosis and we inhibited in two ways...
GvHD causes the cell death of intestinal stem cells. And we investigated a protein that’s called receptor interactive protein one, RIP1, which is involved in cell death. This protein, when is activated, it causes both apoptosis and necroptosis in the intestinal stem cells.
And we study an in vivo model as well as an in-vitro model where we inhibit this protein. And we saw that in the in vivo model this increased survival and alleviates the inflammation in the mouse and also in our in vitro model in intestinal organoids this the inhibition of RIP1 rescues organoids from apoptosis and we inhibited in two ways. One is genetically so we just have a mouse that are mutant in this rip1 protein. So the protein is permanently inactivated. And then we use did it also pharmacologically where we use a compound that inhibits RIP1 that that’s pretty much and we saw this rescue.
Part of the reason that we are so interested in this particular pathway is that all of the drugs that we use at the moment to prevent and treat GvHD are immunosuppressive. And these immunosuppressive drugs are used at a time when the immune system of the patient is reconstituting. And so they’re very vulnerable to infections. So when you add additional immunosuppression to someone who’s already vulnerable to infections, you can you can actually get fatal infections that are a major cause of mortality after transplant. And this pathway does not involve, as far as we can tell, it does not involve any immunosuppression. So we’re essentially protecting the GI tract that is the most vulnerable of the GvHD target organs. And we’re using a non immunosuppressive strategy so that we hope that we can get a benefit from protecting or treating GvHD without increasing the risks of infections. And as Mariano said, we’ve already looked at the graft-versus-leukemia effect in our mouse models and shown that it does not have an effect there. So we are we are very excited about this possibility because it really opens up a new class of drug, which is this non immunosuppressive approach to GvHD. And I think that that’s why we’re going to have a clinical trial that’s already open and is ready to accrue patients. And we believe that this is one of the ways forward for our patients with GvHD which is less of a problem after transplant, but still is a significant problem for a large minority of patients.
