Assuming FDA approval, aGvHD market could be bigger than I initially thought, especially with label extension for chronic adult GvHD.
Interesting point made that chronic GvHD has similarities with autoimmune diseases. This has implications for any autoimmune disease that doesn't respond to conventional therapy. Given the safety profile of mscs, MSB's aGvHD product could be used off label on compassionate grounds for less common autoimmune diseases such as Still's and SLE. Also, given the similarity between IBD and GvHD when there's GI involvement, it could be used for bowel rescue in IBD patients unlikely to survive surgery. Infliximab, the most popular biologic for IBD, has been used in SR GvHD with some success for gut but not the liver. MSB's product is more potent as it's shown efficacy in both. GvHD can attack the connective tissue. RA is a disease of the connective tissue and in severe cases, is a multi organ attack involving the gut, liver, even lungs, as can be GvHD.
Children can present with highly aggressive disease and there's a tendency to fight fire with fire. I believe this is the wrong strategy. In IBD, for example, you can take the worst possible case and all you have to do is tip the balance. Wolfgang Lutz MD, a highly respected physician, used dietary therapy in IBD patients who had failed conventional treatment. He also took pediatric cases and he didn't shy away from the word 'cure'. Dr Suskind from Seattle CH uses the Specific Carbohydrate Diet (the original celiac diet) in IBD patients and has recently published a study on it. The catch is (and it's a big one) that these diets require a lot of discipline and while response can be fast, a cure can take a long time.
The growing interest in dietary therapy and fecal transplant in mainstream medicine shows receptiveness to the idea of using the body's own devices to effect a cure. This fits with the more subtle approach of stem cells. The key for me is the consensus we seem to be moving towards that the MSCs start off a healing process (rather than become anything). as SI said years ago.
As doctors become familiar with MSB's product for aGvHD in the real world, I wonder if they might start to give it first line due to concerns that suppressing the immune system too broadly risks infection or compromising the graft v cancer. I've long had a suspicion that steroids might play a role in causing chronic disease. The biggest predictor of chronic GvHD is prior acute GvHD. I'm assuming patients with cGvHD will have had steroids first line for aGvHD.
Inflammation is a precursor to all disease, specifically gut inflammation. Steroids put out inflammation fast but I'm wondering if it's so fast the mucosa doesn't get a chance to fully heal; it churns away at a low level and there isn't that microscopic healing. In contrast, where the body is supported to take care of the healing, it's more thorough, particularly when it comes to children: Dr Robert Canani MD concluded that exclusive nutritional therapy in children with active Crohn's Disease was 'markedly more effective than steroids in producing healing of mucosal inflammation'.
The focus in medicine is on the microbiome. If leaky gut is the mother of all immune diseases, that calls into question the use of steroids and methotrexate, which can damage the lining of the gut. As anti-inflammatory agents, BM MSCs may have the advantage here in that they may induce repair by signalling to the intestinal stem cells.
I wonder what the survival rate would be if children were given MSC-100-IV right after diagnosis of GvHD? At the same time these children were started on the Specific Carbohydrate Diet or similar (or in cases of severe gut inflammation, enteral nutrition for 6 weeks then kicking into the SCD). More diverse gut flora is linked to greater survival rates in GvHD and probiotic food (the corner stone of the SCD) is most potent.
I also wonder if children presenting with any raging autoimmune disease were given the exact same therapy as above, could they be cured for ever? What you do in the beginning with children is very important and my concern is that the use of broad immune suppressants in autoimmune diseases could reduce the chance of a cure.
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