My last post introduced the large-scale publicly funded clinical trial called BAMI (the effect of intracoronary reinfusion of Bone marrow-derived mononuclear cells on all course mortality in Acute Myocardial Infarction). That post focused on the role of the public purse in funding such trials and concluded that public monies have a major role to play in what companies would consider “not fundable”.
Since clinical trials are enormously expensive, however, it makes the choice of trial to run/fund incredibly difficult and important. The BAMI trial proposes to take whole bone marrow cells from patients who have had a heart attack and transplant them into the hearts of the patients with the hope that these cells will prevent people from re-hospitalization and/or death. Interestingly, the BAMI trial is billed as a stem cell therapy, when in reality it is a hodge-podge of un-fractionated cells that are injected into the heart. Cell therapy, yes. Stem cells, maybe not…
Not there to stay
When we hear about stem cell trials, we often think of permanent cures where the stem cell population(s) replaces damaged stem cells and operates as normal (e.g., as in the case of successful bone marrow transplantations where donor cells repopulate the recipient forever). I don’t think it is likely that the cells in the BAMI trial will be setting up shop in the hearts of patients – but one never knows and it would be very interesting to see if cells are still present at the two year endpoint. Present or not, if these cell suspensions achieve the 25% reduction in mortality and 15% reduction in re-hospitalization, then it may be worth it despite the lack of permanence.
No idea how it works
Even for someone who has trained in the stem cells and regenerative medicine field for 10 years now, it is difficult to imagine how this (stem) cell therapy might work and what the underlying mechanism of action would be. If anything, I think the benefit would come from the other bone marrow cells injected (the non-stem cells) as a sort of directed delivery of key regenerative molecules or cells (e.g., cytokines, immune cells). These molecules may support tissue healing, they may prevent further damage, they may inhibit scarring, but realistically, we simply do not know what they will do and it’s a bit of a cowboy experiment when the data from previous trials are not exactly a ringing endorsement of promised success.
The past likely predicts the future
The only trial I could find, that had any indication of modest effects, was the TAC-HFT trial (clinicaltrials.gov identifier NCT00768066) showing that “the 1-year incidence of serious adverse events was 31.6% for mesenchymal stem cells, 31.6% for bone marrow cells, and 38.1% for placebo controls”. This is a marginal decrease in adverse effects, and the trial only enrolled 65 patients.
On the other hand, the majority of completed studies lack strong positive data (as was also highlighted this Nature News article last week) including:
- TIME study: No significant effect (120 patients) NCT00684021
- The late TIME study: No improvement in global/regional heart function at 6 months (87 patients) NCT00684060
- FOCUS: In chronic heart failure patients, no improvement in heart function or oxygen consumption (92 patients) NCT00824005
- FOCUS-HF: In chronic heart failure patients, BM cell transplantation is safe and improves symptoms, quality of life, and possibly perfusion. (30 patients) NCT00203203
- CARDIO-133: Intramyocardial injection of CD133+ BMC has no relevant effect on global LV function and heart failure symptoms (60 patients) NCT00824005
Not all doom and gloom
Despite these suggestions that this therapy will not benefit patients, the really good news is that the BAMI trial is well-designed, has clear and defined endpoints that are easy to assess (mortality and re-hospitalization) and is unlikely to be damaging to patients since they are receiving their own cells. Moreover, the trial at its conclusion will have developed several protocols that will be useful to the wider community considering future cell therapies. These include standardized methods for bone marrow cell collection and preparation for autologous transplantation into the heart.
Most importantly, the trial is very large (3000 patients) and statistically well-powered meaning that it should really put the question as to whether there is any benefit to the test. A few years from now, we should have a good sense of whether there is something interesting happening and maybe then scientists might invest some energy into figuring out how and why it might work.
Latest posts by David Kent (see all)
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- Tip of the iceberg? Scary stuff from international stem cell clinics - August 2, 2016
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