Cardiac stem cells in ischemic cardiomyopathy – an update of SCIPIO trial

by Alexey Bersenev on September 25, 2012 · 0 comments

in Uncategorized

Cardiac diseases can provide a huge potential market for cell therapies. There are 2 key components for success: (i) unmet medical need and (ii) large patients population. That’s why many companies are jumping into the field. They are sniffing a potential cell therapy blockbuster.

Recently, I’ve written about some results of randomized clinical trials, assessing bone marrow cells in acute myocardial infarction. The results are very heterogeneous and can’t provide solid conclusions today. But there are other cardiac diseases and there are other types of cells. I saw a few opinions about potential advantages of cardiac progenitors over bone marrow cells. There are 2 currently ongoing autologous trials, which are assessing cardiac progenitors cells in cardiomyopathy and heart failure – SCIPIO and CADUCEUS. Both studies completed Phase 1 and reported results. You can learn results of CADUCEUS from here and here. Today, I’ll focus on the latest update from SCIPIO trial.

One of the advantages of SCIPIO trial is a time point for cell therapy = 4 months after CABG surgery. The rational behind is the notion that CABG alone can give spontaneous improvement within first 4 months after procedure. So, this approach can clearly dissect impact of cell therapy from CABG. The patients sign consent form during 2 weeks after CABG, then re-evaluated 4 months later and if eligible, undergo cell transplantation.

Cardiac c-Kit+ progenitor cells were isolated from frozen tissue fragments, which were harvested and dissected on a day of CABG. Cells were injected intra-coronary arteries at max dose = 1 million.

The first preliminary report from SCIPIO trial was published last year in Lancet:

16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001).

The enrollment was concluded last year. Total 20 and 13 patients were treated in “cells” and “control” groups respectively. Now, trialists are collecting data for 1- and 2-year outcome and preparing to launch Phase 2. Last week, updated one year follow-up data were reported in Circulation. The main feature of updated report was a cardiac magnetic resonance (CMR), which was used for assessment of cardiac function and infarct size:

In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5±1.6% to 35.1±2.4% [P=0.004, n=8] and 41.2±4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory.

LV nonviable mass decreased even more (−11.9±2.5 g [−49.7%] at 4 months [P=0.001] and −14.7±3.9 g [−58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6±5.1 g at 4 months after CSC infusion [P=0.055] and +31.5±11.0 g at 12 months [P=0.035]).

I highlighted 1-year outcome data, because persistence of efficacy is extremely important. You won’t do these kind of procedures repeatedly every 2-3 years. As Roberto Bolli has mentioned in video below, they observed efficacy persistence for 2 years now. That’s very good news!

Now, I’m not sure why ratio necrotic/ viable myocardium after cell infusions is not close to 1:1, but authors attempted to calculate regenerative potential of therapy:

Based on the decrease in infarct size, and assuming that 90% of the regenerated myocardium is composed by cardiomyocytes and the volume of differentiated myocytes is ≈20 000 μm 3 [20], it can be estimated that ≈294×106 and 415×106 cardiomyocytes were generated within the scar at 4 and 12 months, respectively.

Were generated from? Could be infused cells or could be resident cardiac stem cells. Nobody knows at this point. But if 1 million of infused cells can boost up to 400-500 millions in vivo, it’s really impressive.

Well, I hope we will get more evidence for scar replacement by viable myocardium from both SCIPIO and CADUCEUS trials. I think, we have many reasons to expect good results from Phases 2. We will eagerly watch how Capricor can commercialize this cardiosphere technology. I wonder if c-Kit+ technique will be picked up from academia and commercialize.

Finally, the recent interview with Roberto Bolli – PI of SCIPIO trial:

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