A team of Irish cardiologists have shown that injecting an insulin-like growth promoter into the hearts of patients who have suffered a severe heart attack can repair damaged cardiac muscle and reduce the risk of future heart failure.
Prof Noel Caplice, Chair of Cardiovascular Sciences at University College Cork, and his cardiologist colleagues at Cork University Hospital successfully tested the growth factor in a clinical trial involving 47 patients who presented at the Cork hospital after experiencing heart attacks.
Prof Caplice said 20 per cent of people who suffer heart attacks have severe ongoing difficulties because of lasting damage to heart muscle even after the best current therapies.
“After you have a heart attack, regardless whether you treat it with a stent or whatever, about 20 per cent of patients go on to have poor remodelling – heart muscle cells die, you get scar tissue forming and the heart tends to expand and dilates, a bit like a balloon, and you get thinned-out heart muscle.
“With that poor remodelling of the heart, the heart as a structure performs much worse, it doesn’t work very well in terms of its function – that leads to a substantial number of those patients going on to suffer heart failure with an increased risk of death,” he said.
Stem cells
However, 10 years ago, Prof Caplice and his team began looking at using stem cells as a means of repairing damaged tissue and they found a protein within the stem cells, IGF 1, previously used to treat congenital dwarfism and growth problems, was leading to the repair of damaged heart muscle.
“IGF 1 acts differently to insulin in that it acts on a different receptor in the body and when we inject it, it gets into the heart tissue and it basically stimulates receptors on the surface of the cardiac cells and in about 30 minutes, it sends a survival signal to the heart muscles cells,” he said.
“What we discovered from the stem cell study was that the concentration of the factor was extremely low so what we did was that we took the purified factor and in studies with pigs we injected them in the context of a heart attack and we found these major remodelling benefits.”
Those animal tests were funded by Science Foundation Ireland but four years ago the Health Research Board came on board and the two bodies provided a €1 million grant to allow the treatment be trialled on humans.
Working with a 25-strong team incorporating cardiologists, radiologists, MRI specialists and nurses, Prof Caplice was able to incorporate the IGF 1 trials into the treatment of patients attending CUH with severe cardiac events and over the past three years have trialled it on 47 patients.
Low-dose preparations
Patients received two different low-dose preparations of insulin-like growth factor or placebo in a randomised double-blinded clinical trial, with results showing those who received the higher dose had improved remodelling of their heart muscle in the two-month follow-up after their heart attack.
Prof Caplice said the CUH trials, the results of which he will present at a European Society of Cardiology conference in Paris on Saturday, were the first use of IGF 1 in human hearts and part of its attractiveness was its low dosage ensuring minimal side effects while improving cardiac structure.
Among the beneficiaries was John Nolan from New Ross who suffered a heart attack in December 2014. "I feel I was blessed to be asked to be involved; I had confidence that good would come from it, in terms of how they explained it to me. Looking back on it now, I feel it was the right choice."
For Prof Caplice, the challenge now is to expand the trials to several hundred patients possibly across different countries and different healthcare systems to see if the IGF 1 treatment is globally applicable which, if proven to be the case, could lead to regulatory approval within five years.