I wrote some time ago that I thought I'd underestimated the role...

I wrote some time ago that I thought I'd underestimated the role of inflammation in CHF. It was amazing to hear SI come out and say it.

I don't know much about CHF but I've been researching autoimmune diseases for the past decade. The importance of an anti-inflammatory agent that isn't cortiosteroids can't be underestimated. I believe there will be a paradigm shift because current therapy is doing harm.

The most harm being done is in paediatrics IMO. Children are not mini adults; they're designed to get better. If you take a sledgehammer to the immune system in childhood, no wonder you end up with a chronic disease. Seattle Children's Hospital has recently confirmed what activists have been saying for two decades: the key role of the microbiome in IBD. Other research has very recently (last year) pointed to the microbiome in RA also. This calls into question the use of heavy immune suppressants that don't address this.

It's quite possible that MSCs don't address the microbiome either. They're described in journals as immunosuppressants but more often ' immunoregulators' or 'immunomodulators'. While I do believe MSCs are immune suppressants, from what I've read in journals (as a layperson), my daughter's research paper and listening to SI, they seem to communicate with the immune system rather than slam it. From a patient perspective MSCs seem to be a more targeted and elegant therapy.

If some bacteria are pro-inflammatory then why not simply change the microbiome by introducing good bacteria? That can be done but it takes a very long time. It's still important to get inflammation under control. Borody used standard drugs prior to fecal transplant because bacteria won't adhere to inflammation. Perhaps this explains the more modest results for FT in IBD versus the miraculous ones in c.diff (virtually 100% cure).

Googling a bit tell you big pharma are getting on the microbiome bandwagon. Far from myopic, they know the zeitgeist is away from drugs and towards more targeted therapies. Frankly, I can't see the pairing of a microbiome tweaker with an immune slammer or something that poisons the body like corticosteroids or the thiopurines. Pharma have developed more targeted anti-inflammatory drugs, such as the JAK inhibitors for RA, but they seem to have come out with bigger sledgehammers that have worse side effects.

Corticosteroids get inflammation under control very quickly but outside of an emergency situation their reign needs to come to an end. The real scandal is the number of patients with inflammatory conditions who are on them long-term. In IBD, it's said that 30% of patients don't respond to biologics. I think this figure is conservative. Even among those who respond, the effect is temporary, which is why biologics are used as a bridge to the thiopurines, which are less safe. IMO the biologics have done a much better job in IBD than RA but patients can build antibodies. In IBD the most popular biologic is Infliximab. Look up the rate of response after the first infusion and then what it drops to after the second.

SI said with reference to RA, that the emergence of biosimilars will lead to more biologic-refractory cases due to switching. That tells me he knows his stuff because the top IBD specialists are warning doctors about the same thing. It's not known how similar the biosimilars are. I'd say biologic refractory cases are higher in RA because switching has already gone on. One interesting area of research is in MSCs ability to enhance the efficacy of immunosuppressants, such as in the case of Rapa. MScs may not even make biologics obsolete but extend their lifespan.

Methotrexate is still widely used in RA because it's usually well tolerated. Doctors explain to patients that it's a low dose and they're not 'on chemo' but patients don't tend to see it that way, especially if they're losing hair. Even side effects that are not life threatening are a big issue to patients. The more targeted drugs, such as the JAK inhibitors, seem to come with worse side effects. Tofacitinib for biologic-refractory RA was refused a licence by the EMA for four years over safety concerns.

Canakinumab was recently touted in the Fairfax media as the 'wonder drug' for heart failure. I'm assuming this is the same one trialled in gouty arthritis? The FDA stopped the trial over safety concerns for a condition that wasn't life threatening. Michael Carome MD from Public Citizen, a consumer watchdog group, said it was dangerous because just a single dose raised the risk of infections. Multiple doses raise concerns about malignancies.

It seems to me that the more effective an anti-inflammatory, the higher the risk of serious side effects. I understand it might not be possible to have a medical therapy that's entirely without side effects but what we currently have is far from acceptable.

Where MSB's science is concerned one poster, who said he was a doctor, said they basically have the same product. I'm not sure about that as I'm still learning about their stem cells, but if that's case, then maybe that's the point as inflammation is a precursor to so many diseases, including cancer. Are MSB stem cells potent anti-inflammatory agents that don't cause long term damage and poison the body? If so, they have something very valuable. I know it's a risk to invest before phase 3 results but I'm satisfied with the evidence and safety profile so far.

IMO the best evidence so far comes from CHF and Temcell.

The independent interim analysis showed efficacy in 270 CHF patients. This is a significant number IMO. I've long seen the application of MSCs in autoimmune conditions but I was sceptical about CHF. Then when I started reading up on MSCs in CHF, I went too far the other way and started expecting too much. If inflammation, however, is a major factor in CHF as recent research points to, then the key will be durability of the heart, which is linked to time.

IMO Temcell growth is a sign of clinical efficacy because it's a tiny market. It's possible to work out how many BM transplants occur in Japan, how many out of those might develop aGVHD (bearing in mind a lot of recent research has gone on into ways to prevent it), what percentage don't respond to corticosteroids. Just because a drug isn't approved for SR aGVHD doesn't mean it doesn't work like switching to Tacrolimus or using Sirolimus. From what I know of doctors, they tend to stick to what they know. I think that, as a novel therapy, a MSC product would start out at the bottom of the list and by then it's got a hard job to do.

Some posters have stated that no partnerships means pharma likely don't see value in MSB science. This would be laughable if we weren't talking about death, multiple non-curative surgeries or surgery that permanently reduces the quality of life and impacts fertility in young women, or side effects like liver damage from chemo drugs or blindness from long-term coritcosteroid use.

I ask these people to check out the science pharma currently see value in. Look at the drugs the FDA has recently approved and found their way onto the market. For a drug to be approved and get on the market, does it simply have to show it's better than nothing? It might even be worse than nothing. I wonder if these critics can think of an aggressively promoted drug developed on an entirely false premise that's generated billions upon billions of dollars in revenue and does bugger all. I can. News of the Hynes and Sultan study recently broke in the UK media, but all of this has been out in the US for a long time.

When I went up against four different "incurable" autoimmune diseases, everything I learned came from activists in the US. The anger and contempt for "modern" medicine took my breath away. CHF statistics over there are truly appalling. If MSB phase 3 results are good, there will be some very influential people in the US who will demand this therapy and I believe they're likely to get what they want.

I'm writing mostly from a patient perspective but that's the point. Medicine is now a consumer driven market and clinicians better make sure they're up-do-date on all the latest therapies because patients will ask about them. The best results IMO come when doctors and patients listen to one another and work together. I don't have a background in science, so if anyone does, please feel free to correct any errors.