When Ottawa researchers publish a paper about a protein that can used to treat heart disease on Tuesday, fellow scientists in California will probably be saying, “Doh!” like Homer Simpson.
The naturally-occurring protein, called cardiotrophin 1, also known as CT-1, can trick the heart into repairing damage and improving blood flow. Therapy using the protein, which the Ottawa researchers have already proved in animal models, will likely be ready for clinical trials in patients with right heart failure and myocardial infarction — heart attack — in two or three years.
With luck, therapy will be available to the general population in about a decade. It might even reduce the need for heart transplants.
About 20 years ago, the California scientists were investigating CT-1 and benefits for heart patients, but they gave up after they learned that CT-1 was also linked to disease. Around 2005, the Ottawa researchers decided to tease out how the mechanisms behind how the protein worked, both positive and negative. They believed the negative effects were compensating for something else.
The Ottawa researchers, including scientists from The Ottawa Hospital, the University of Ottawa, the University of Ottawa Heart Institute and Carleton University and private industry, have worked to understand the signalling pathways, genes and cellular processes associated with CT-1. It was a long road, and along the way there were a lot of blind alleys, said Lynn Megeney, the senior author on a paper published Tuesday in the journal Cell Research.
When part of the heart dies, its remaining muscles try to adapt by getting bigger. But this happens in a dysfunctional way, and it doesn’t actually help the heart pump more blood. CT-1 helps the muscles to grow in a more healthy way and stimulates blood vessel growth around the heart, improving its ability to pump blood.
This process happens naturally during pregnancy and when athletes exercise. After the baby is born or the athlete stops exercising, the heart returns to its original state, said Megeney, a senior scientist at The Ottawa Hospital and professor at the University of Ottawa.
The researchers have tested CT-1 on animal models with right heart failure. In humans, more than 40 per cent of the total heart failure population has right heart failure, said Megeney. It’s a growing epidemic in North America and one of the leading causes of death and disability in high-income nations.
“The medical world has become quite proficient at treating heart failure. It’s good at helping people with classic congestive heart failure. But the problem is that these medications don’t work on right heart failure.”
For some patients, the only option is a heart transplant.
CT-1 can “beneficially remodel” the right side of the heart, he said. While exercise could theoretically have the same benefits, people with heart failure usually can’t exercise. “Treatment with CT-1 might get them to that point.”
In the research with mice and rats, CT-1 was delivered with a mini-pump about the size of a tablet inserted under the skin. A similar gadget would likely work with people.
Treatment is not a permanent solution. So far, about two weeks of treatment have proven to be beneficial for about two months after treatment stops. The researchers still need to figure out the minimum dose to get the maximum effect, but CT-1 treatment could replace a cocktail of drugs, said Megeney.
Dr. Duncan Stewart, a cardiologist, co-senior author of the paper and executive vice-president of research at The Ottawa Hospital, called the experimental therapy “very exciting”, especially since it shows promise for both right and left heart failure. Megeney and Stewart have patents pending for the use of CT-1 to treat heart conditions.
“Currently, the only treatment for right heart failure is a transplant,” said Stewart. “And although we have drugs that can reduce the symptoms of left heart failure, we can’t fix the problem, and left heart failure often leads to right heart failure over time.”
Score one for basic science.
“This derives from simple, basic research on the cellular and molecular mechanisms that make heart muscle grow,” said Megeney, who has already presented the findings at international meetings. “People hadn’t pushed to understand the process. It was under the radar for a long time.”
Original article written by Joanne Laucius can be found here.