November 7, 2012
Studies On Stem Cell Therapy After Heart Attack Show Mixed Results
April Flowers for redOrbit.com - Your Universe OnlineUniversity of Louisville and Brigham and Women's Hospital, reported "holy grail" results for a Phase I clinical trial: marked sustained improvement in all patients with zero adverse effects.
Roberto Bolli, M.D., of the University of Louisville and Piero Anversa, M.D., of Brigham and Women's Hospital presented data from their groundbreaking research in the use of autologous adult stem cells with patients who had previous heart attacks in a Late-Breaking Clinical Trial session.
The researchers report that all patients receiving the stem cell therapy showed improved heart function after two years, with an overall 12.9 absolute unit increase in left ventricular ejection fraction (LVEF). LVEF is a standard measure of heart function that shows the amount of blood ejected from the left ventricle during a heartbeat. They saw no adverse effects from the therapy. In fact, nine patients showed evidence of myocardial regeneration — new tissue replacing formerly dead tissue killed by heart attack — in MRI scans.
"The trial shows the feasibility of isolating and expanding autologous stem cells from virtually every patient," said Bolli, who is the Jewish Hospital Heart and Lung Institute Distinguished Chair in Cardiology and director of the Institute for Molecular Cardiology in the Department of Medicine at UofL. "The results suggest that this therapy has a potent, beneficial effect on cardiac function that warrants further study."
"In all patients, cells with high regenerative reserve were obtained and employed therapeutically," said Anversa, professor of Anesthesia and Medicine at Brigham and Women's Hospital and Harvard Medical School. "Our efforts to carefully characterize the phenotype and growth properties of the cardiac stem cells may have contributed to these initial positive results."
The Stem Cell Infusion in Patients with Ischemic CardiOmyopathy, or SCIPIO, trial was a randomized open-label trial of cardiac stem cells (CSCs) in patients who were diagnosed with heart failure following a myocardial infarction and had a LVEF of 40 percent or lower. A normal LVEF reading is 50 percent or higher.
The CSCs, referred to as "c-kit positive" cells because they express the c-kit protein on their surface, were harvested from 33 patients during coronary artery bypass surgery. The stem cells were then purified and processed so that they could multiply, and once an adequate number was produced — about one million for each patient — they were reintroduced into the region of the patient's heart that suffered scarring during the heart attack.
At four months after infusion, the researchers report that LVEF increased from 29 percent to 36 percent for 200 patients. On average, the 13 control patients who did not receive a CSC infusion showed any improvement.
AT both the one and two-year mark, the beneficial effects of the CSCs persisted. LVEF increased by 8.1 percent and 12.9 percent respectively.
Of the nine patients who received MRI scans, there was a profound reduction in the size of the infarct, that area of the heart that is dead tissue as a result of the heart attack. Prior to treatment, the infarct size was 33.9 grams, and at 18.2 at two years. The MRI also revealed an increase in viable left ventricle tissue, from 146.3 to 164.2 grams. The rest of the study participants were not able to undergo MRIs because of previously implanted devices which interfered.
Jim Dearing of Louisville showed no trace of the two heart attacks he suffered prior to participating in the trial. His ejection fraction went from 38 percent to 58 percent and his heart is working normally, according to Echocardiograms performed in 2011 and 2012.
"Anyone who looks at his heart now would not imagine that this patient was (ever) in heart failure or that he had a heart attack," Bolli said. "What's striking is that we are seeing what appears to be a long-lasting improvement in function," Anversa said.
The plan is to follow the study cohort for two additional years, and expand the original research.
"The findings warrant larger, phase 2 studies," Bolli said. "If the larger studies continue to confirm our findings, we potentially have a cure for heart failure because we will have something that conceivably, for the first time, actually regenerates dead heart tissue."
The second clinical study, presented by Jay Traverse, MD of the Minneapolis Heart Institute Foundation, shows that administering autologous stem cells obtained from bone marrow either 3 or 7 days following a heart attack did not improve heart function six months later.
The results of the Transplantation In Myocardial Infarction Evaluation, or TIME, trial mirror a previous, related study (LateTIME). LateTIME found that autologous bone marrow stem cell therapy given 2-3 weeks after a heart attack did not improve cardiac recovery. Both studies were supported, in part, by the National Institutes of Health (NIH) and carried out by the Cardiovascular Cell Therapy Research Network (CCTRN).
"The data presented by TIME do much to advance stem cell therapy research," said Jay Traverse, MD of the Minneapolis Heart Institute Foundation and Principal Investigator of this study. "While this study did not provide a demonstrated cardiac benefit after six months, we still learned a great deal. Together, TIME and Late TIME have shown that stem cell therapy is safe, and they have set a baseline in terms of quantity of stem cells, type of stem cells, and severity of heart attack."
The 120 participants, with an average age of 57, were enrolled between July 2008 and February 2011. They all had moderate to severe impairment in their left ventricle and had undergone coronary stent placement as treatment for the heart attack. They were assigned to one of four possible groups; day 3 stem cell, day 3 placebo (inactive cells), day 7 stem cell, or day 7 placebo. Stem cells from the bone marrow of each patient were processed and purified to ensure a uniform dose of 150 million stem cells for each patient.
After six months, heart improvement was assessed by measuring the percentage of blood that gets pumped out of the left ventricle during each contraction (left-ventricular ejection fraction, or LVEF). No significant differences between the change in LVEF readings at the six month follow-up were found in either the Day 3 or Day 7 stem cell groups when compared with placebo or with each other. Across the board, the groups had about a 3 percent improvement in LVEF, however, the researchers found that younger patients randomized to Day 7 had greater improvement in their LVEF compared to their placebo counterparts.
"The lack of six-month improvement seen for TIME and, prior to that, LateTIME, does not mean stem cell therapy is not a viable post-heart attack strategy," said Traverse. "Because we have this data we can start to address some parameters; for example this therapy may work better in younger people, or maybe we need to use cells from healthy volunteers (allogeneic) since their cells may provide greater therapeutic benefit. There will also be upcoming studies using novel cell types which we look forward to using in future clinical trials."