I think this product has the potential to get even better results in clinical practice. If used first-line maybe there would be fewer infections.
Also, the focus is now on intestinal permeability and the microbiome in GvHD. Steroids are not associated with good mucosal healing. Our cells target both inflammation and promote healing (SI mentioned a 'two-step process'). This imo could provide a better environment for probiotics (safest and most potent imo is in the form of food) to take hold.
Doctors might worry about holding off on the steroids because of their ability to get things under control very quickly, especially with gut inflammation which has the highest death rate.
If so, there's something else that could be given at the same time that kicks in (from my experience within 24h) that's totally benign and has equal power to steroids.
Exclusive enteral nutrition (EEN) is enjoying a revival in Europe. It's recommended first-line in pediatric Crohn's Disease (IBD and GvHD have similarities when the GI tract is involved) because it delivers superior mucosal healing to steroids. Current thinking is that it favourably alters the microbiome.
EEN is such a benign therapy there's a prevailing view that it only works for mild/moderate disease. From my experience, this is not so. It's even been used in juvenile ideopathic arthritis. These were not mild cases. (Berntson et al 2016)
The big drawback of EEN is it can't be kept up for long (usually six weeks) and its effects often wear off quickly once stopped, which is why it makes a good adjunct therapy while you wait for something to kick in or you have an idea to kick into something else.
I was interested to come across a paper by Dr Carpenter (Blood 2017) who, according to an article posted here, obtained MSB's product for a child on compassionate grounds. This paper is mainly about the importance of intestinal permeability and the microbiota in GvHD. Greater understanding of this area could lead to "a multifaceted intestinal GVHD supportive care package. "Greater use of EEN" is one possibility mentioned by Dr Carpententer. I was also interested to read about the possibility of human breast milk.
Potential Implications for CHF
We have good results for gut, liver, skin, why not then any organ? Despite thinking along these lines, I always felt less confident about CHF than GvHD. The heart seemed like such a difficult task and this area has been dogged by many negative results.
It seems, though, the outlook is looking brighter just in the last year or two:
"The limit in treatments for CVD is because of the previously prevailing viewpoint that the heart is a terminally differentiated organ with little to no regenerative capacity. This paradigm shifted after the identification of a small resident population of multipotent cardiac stem cells (CSC), reframing the heart as an organ with the capacity for self-renewal."(Banerjee et al. Circulation Research 2018)
"MSCs communicate with CSCs leading to reduced infarct size, and improved cardiac performance."
"Hatzistergos et al. have shown that MSCs impart profound effects on CSCs" (Fish, 2015)
A poignant video was posted here of a young man with a LVAD who was delighted to be able to run again. I was quite sure such an impressive improvement was down to MSB's stem cells but I wondered about older patients. I was encouraged, however, to learn there's not necessarily a difference in response:
"Importantly, older individuals did not have an impaired response to MSC therapy." (Golpanian et al 2015)
If the mechanism is the same and problems such as delivery and dosing are worked out, then imo it all hinges on how potent a company's cells are and whether manufacturing consistency can be maintained and we have our answer to that.
Please feel free to correct any errors of science as I'm writing from a patient's perspective. We are the end users after all.
All IMO. Good luck to all holders
MSB Price at posting:
$1.87 Sentiment: Hold Disclosure: Held
(20min delay)