Dr Peter Henriksen
Clinician researcher and consultant cardiologist at the Edinburgh Heart Centre, Royal Infirmary of Edinburgh.
Dr Peter Henriksen is an MRC-funded researcher who is collaborating with a small biotech start-up to conduct a clinical trial of whether a particular protein can help the heart recover more quickly after surgery. He is funded by an MRC Industry Collaboration Award (MICA).
It’s not unusual for biomedical PhD students to dream that their long hours at the lab bench will one day pay off in the form of a clinical trial. What’s more unusual is conducting that clinical trial yourself.
Dr Peter Henriksen did a PhD at the MRC Centre for Inflammation Research between 1999 and 2002, investigating whether a naturally-produced protein called elafin could reduce potentially damaging inflammatory responses from a type of blood vessel cell and a type of white blood cell.
Now he’s taking the same protein through an MRC-funded clinical trial in patients undergoing coronary artery bypass surgery, where blood flow to the heart is improved by using arteries or veins from other parts of the body to shortcut around parts of the artery that have furred up.
He’s trying to find out whether elafin can help protect the heart from ‘reperfusion’ injury, a type of inflammatory injury caused by cutting off the blood supply to the heart during surgery and then refilling it afterwards. The more inflammatory injury, the more likely a patient is to need to stay in hospital, or perhaps even to suffer heart failure.
From lab to clinic
During his PhD working in Dr Jean-Michel Sallenave’s group Peter found that if elafin was present in a higher than usual concentration, it dampened the inflammatory response. At the same time, work within Sallenave’s and other groups found that elafin could protect animal models from inflammatory injury.
Peter completed his clinical training in cardiology and was appointed as a consultant but, finishing the write up of his PhD, was still thinking about elafin.
“I was thinking about the next step. The combination of what I knew from my work and the results of the pre-clinical [animal] studies meant the time was right for translational studies. Things were coming together at once.”
The body naturally produces elafin but the protein’s promising effects in Peter’s work and the animal studies occurred when it was present in large quantities. Unfortunately for Peter, elafin is difficult to make in the lab because of its unusual folding pattern.
However, around the time that Peter was thinking about clinical trials with elafin, a research group in Germany was harnessing new developments in protein technology to make yeast produce the correctly-folded protein. The group, led by Professor Oliver Wiedow, set up a spin out company, Proteo, to supply clinical-grade elafin. The company also carried out the first phase I studies required to show that it is safe to give to people.
“It’s very exciting to be in this position and to be at the point where something that I worked on ten years ago in the tissue culture labs is now being administered to patients. It’s a wonderful thing,” says Peter.
Twenty-six patients have enrolled in the trial so far, with 80 due to have been treated when it finishes. As the bypass surgery begins, the patient is randomised to either an infusion of elafin or saline placebo. After the surgery, blood tests are taken for 48 hours to test for levels of particular ‘biomarkers’ — substances used to measure biological processes — that indicate how much muscle injury has occurred or how much of an inflammatory response there has been. A bolt-on grant from Chest Heart & Stroke Scotland is funding MRI scanning of patients to look for inflammatory heart muscle injury.
The realities of drug development
Getting the research into a clinical trial would have taken much longer — or not happened at all — if it wasn’t for the MICA funding for academic and industry researchers to work together, says Peter.
“This is happening because a funding body like the MRC is prepared to look at the reality of drug development and the biotech industry. There may be some biotech firms that are extremely wealthy and can pick and choose what they want to fund, but I don’t believe this to be the case for the small company like Proteo.”
“The industry collaboration has been key to the relatively short period of time it’s taken for this trial to take place,” says Peter.
If the trial shows that elafin reduces the biomarkers of muscle injury and inflammation, the next step will be to show that its effect is meaningful to patients — that they stay in hospital for less time, for example.
This kind of inflammatory injury also happens during treatment of heart attacks and stroke and after other types of surgery, including organ transplantation, says Peter, so elafin could be useful in many other areas.
For now, Peter is awaiting the results of the current trial, and trying not to give in to the temptation to read positive signs into the blinded results that he sees.
“Some of the trial participants are my patients, and some of them recover really quickly — it’s very tempting to suggest that these might be the ones who were treated with elafin, but we’ve no way of knowing yet. Our fingers and toes are crossed that we’re able to prove what we’ve been seeing in cell and preclinical studies.”
Find out more about the MRC working with industry.
Published March 2012