text: 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.” ||||| A protein called cardiotrophin 1 might be an effective treatment for heart failure, according to researchers who found that it tricks the heart into growing in a healthy way. This growth is reversible, similar to that which occurs in response to endurance exercise or pregnancy. 
   
   
   
   Researchers from Canada have shown that it may be possible to trick the heart into growing healthily, without having to exercise. Researchers from Canada have shown that it may be possible to trick the heart into growing healthily, without having to exercise. 
   
   The team, including members from the Ottawa Hospital and the University of Ottawa in Ontario, Canada, reports the finding in the journal Cell Research. 
   
   The study paper also describes how, in animal models of heart failure, cardiotrophin 1 (CT1) promotes heart repair and improves blood flow. 
   
   Heart failure is a serious condition in which the heart cannot pump enough oxygen-rich blood to meet the needs of the body and its organs. The condition commonly results from heart muscle damage following a heart attack, the main cause of which is coronary artery disease. 
   
   There are around 26 million people living with heart failure worldwide, and numbers are rising. 
   
   Step forward in regenerative medicine 
   
   The outlook for patients diagnosed with heart failure are poor; their survival rates are worse than those of patients with breast, prostate, and bowel cancer. 
   
   In the United States - where around 5.7 million adults are living with heart failure - around half of patients die within 5 years of being diagnosed. 
   
   If heart failure is diagnosed and treated early, it is possible to improve survival and quality of life. Treatment usually consists of drug therapy, reducing dietary sodium, and exercising regularly. 
   
   The new study represents a step forward in a regenerative medicine approach to the treatment of heart failure, where the aim is to treat or even cure the disease by regrowing damaged tissue or restoring function. 
   
   Co-senior study author Lynn Megeney, a professor at the University of Ottawa, explains that when part of the heart dies - as it does in heart failure - "the 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." 
   
   But he says that, in animals with heart failure, they found that CT1 caused the heart muscles to "grow in a more healthy way," and it also stimulated the heart to grow new blood vessels. "This actually increases the heart's ability to pump blood, just like what you would see with exercise and pregnancy," he adds. 
   
   CT1 investigated in several models 
   
   Prof. Megeney and team investigated the effects of CT1 in laboratory-grown heart muscle cells, rats, and mice. They also compared the effects of CT1 with those of phenylephrine (PE), which is a drug that stimulates the "bad kind of heart growth," such as the harmful, irreversible enlargement that occurs in heart failure. 
   
   The researchers found that, when treated with CT1, heart muscle cells grow into longer, healthier fibers, whereas treatment with PE just results in wider growth. Also, with CT1, the new heart muscle tissue formed with new blood vessels alongside, which helps the heart to pump better. PE did not have this effect. 
   
   Furthermore, the heart growth that occurs with CT1 is reversible; when treatment stops, the organ returns to its original size, as it does when exercise stops or after pregnancy. The unhealthy heart growth that results from PE, on the other hand, is irreversible; when treatment stops, the heart remains dysfunctionally enlarged. 
   
   In two animal models of heart failure - one caused by heart attack, which damages the left side of the heart, and the other caused by pulmonary hypertension, or high blood pressure in the lungs, which damages the right side - CT1 treatment led to "dramatic improvements" in heart function. 
   
   Finally, although both CT1 and PE use the "cell suicide," or apotosis, molecular pathway to trigger heart muscle growth, CT1 showed superior ability to control the pathway. 
   
   The team is excited by these findings because, if they translate to humans, they could vastly improve the prognosis for patients with heart failure. 
   
   Promising for both types of heart failure 
   
   Co-senior author Prof. Duncan Stewart - cardiologist, senior scientist, and executive vice president of research at the Ottawa Hospital - explains that, at present, the "only treatment for right heart failure is a transplant." 
   
   "And although we have drugs that can reduce the symptoms of left heart failure," he adds, "we can't fix the problem, and left heart failure often leads to right heart failure over time." 
   
   The researchers are hopeful that CT1 will work in humans with heart failure because it did so in several animal models of the condition. 
   
   They also point out that, while in theory, exercise is an obvious way to reap the benefits that CT1 appears to offer, this route is not open to people with heart failure, who can only exercise in a limited way. 
   
   Profs. Megeney and Stewart already have patents pending for using CT1 to treat heart problems, and they hope to partner with others to test the protein in human patients. 
   
   Nevertheless, they say that it will be several years, even if the tests are successful, before the treatment is ready for widespread clinical use. ||||| Researchers have discovered that a protein called cardiotrophin 1 (CT1) can trick the heart into growing in a healthy way and pumping more blood, just as it does in response to exercise and pregnancy. They show that this good kind of heart growth is very different from the harmful enlargement of the heart that occurs during heart failure. They also show that CT1 can repair heart damage and improve blood flow in animal models of heart failure. The results are published in Cell Research. The research team is from The Ottawa Hospital, the University of Ottawa, the University of Ottawa Heart Institute and Carleton University. 
   
   Heart failure is a leading cause of death and disability in high-income countries and a growing problem around the world. It occurs when the heart can't pump enough blood through the body, often because a heart attack has damaged the heart muscle tissue. 
   
   "When part of the heart dies, the 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," said Dr. Lynn Megeney, senior author of the study and a senior scientist at The Ottawa Hospital and professor at the University of Ottawa. "We found that CT1 causes heart muscles to grow in a more healthy way and it also stimulates blood vessel growth in the heart. This actually increases the heart's ability to pump blood, just like what you would see with exercise and pregnancy." 
   
   Dr. Megeney and his colleagues conducted a variety of studies in mice, rats and cells growing in the lab. In addition to CT-1, some of the studies involved a drug called phenylephrine (PE), which is known to cause the bad kind of heart growth. They found: 
   
   Heart muscle cells treated with CT-1 become longer, healthier fibres, while those treated with PE just grow wider. 
   
   CT-1 causes blood vessels to grow alongside the new heart muscle tissue and increases the heart's ability to pump blood, while PE does neither. 
   
   When CT-1 treatment stops, the heart goes back to its original condition, just like it does when exercise or pregnancy end. However, the dysfunctional heart growth caused by PE is irreversible. 
   
   CT-1 dramatically improves heart function in two animal models of heart failure - one caused by a heart attack (affecting the left side of the heart) and one caused by high blood pressure in the lungs (pulmonary hypertension, affecting the right side of the heart). 
   
   Both CT-1 and PE stimulate heart muscle growth through a molecular pathway that has traditionally been associated with promoting cell suicide (apoptosis), but CT-1 has a better ability to control this pathway. 
   
   "This experimental therapy is very exciting, particularly because it shows promise in treating both left and right heart failure," said Dr. Duncan Stewart, a cardiologist, senior scientist and co-senior author on the paper who is also Executive Vice-President of Research at The Ottawa Hospital and a professor at the University of Ottawa. "Currently, the only treatment for right heart failure is a transplant. 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." 
   
   "An intriguing aspect of this research was how human CT1 was able to promote a healthy growth response in multiple animal models," said co-author Dr. Patrick Burgon, scientist at the University of Ottawa Heart Institute and assistant professor at the University of Ottawa. "This suggests the action of CT1 is universally conserved and puts us much closer to therapy." 
   
   The researchers also note that while exercise could theoretically have the same benefits as CT-1, people with heart failure are usually limited in their ability to exercise. 
   
   Dr. Megeney and Dr. Stewart have patents pending for the use of CT-1 to treat heart conditions and they hope to develop partnerships to test this protein in patients. If this testing is successful it will take a number of years for the treatment to become widely available. 
   
   ### 
   
   Full reference: Cardiotrophin 1 Stimulates Beneficial Myogenic and Vascular Remodeling of the Heart. Cell Research advance online publication 8 August 2017; doi:10.1038/cr.2017.87 Mohammad Abdul-Ghani, Colin Suen, Baohua Jiang, Yupu Deng, Jonathan J. Weldrick, Charis Putinski, Steve Brunette, Pasan Fernando, Thomas T. Lee, Peter Flynn, Frans H. H. Leenen, Patrick G. Burgon, Duncan J. Stewart, and Lynn A. Megeney http://www. nature. com/ cr/ index. html 
   
   Funding and other acknowledgements: Dr. Megeney and Dr. Stewart are part of The Ottawa Hospital's Regenerative Medicine Program, which includes the Sprott Centre for Stem Cell Research and the Sinclair Centre for Regenerative Medicine. This research was possible because of generous support from the community for Regenerative Medicine Research. This study was also supported by the Canadian Institutes of Health Research, the Ontario Research Fund, the Heart and Stroke Foundation of Canada and Fate Therapeutics. Fate also contributed scientifically to this research. 
   
   Media contact: Amelia Buchanan; ambuchanan@ohri.ca; Office: 613-798-5555 x 73687; Cell: 613-297-8315 
   
   About the partner institutions: The Ottawa Hospital is one of Canada's largest learning and research hospitals with over 1,100 beds, approximately 12,000 staff, over one million patient visits per year and an annual budget of over $1.2 billion. Along with the University of Ottawa Heart Institute, we are proudly affiliated with the University of Ottawa, one of Canada's top 10 research universities. The Hospital and Heart Institute were awarded exemplary status from Accreditation Canada and together with the University, have developed a roadmap for cardiovascular research excellence in the region.
target: – Scientists in Canada say they've found a way to trick the heart, making it behave as if it were the beneficiary of exercise even if no exercise was able to be done. According to a study in Cell Research, the Ottawa researchers discovered that protein cardiotrophin 1 (CT1) can fuel healthy heart growth, repair heart damage, and cause the heart to pump more blood in cases of left heart failure, as a result of heart attack, and right heart failure, as a result of high blood pressure in the lungs, reports Medical News Today. It's a big deal since medications used to treat left heart failure don't work on right heart failure, which usually requires a heart transplant, per a release. Exercise can be beneficial because it boosts the heart's ability to pump blood, but "people with heart failure usually can't exercise," researcher Lynn Megeney tells the Ottawa Citizen. The heart usually responds by expanding, irreversibly, in an unhealthy way. But that's why CT1 is "very exciting," Megeney says. It "causes heart muscles to grow in a more healthy way and it also stimulates blood vessel growth in the heart," increasing blood flow just like with exercise. And just like with exercise, the heart returns to its original size afterward. Megeney says the discovery could lead to fewer heart transplants, but he says it could be two or three years before researchers begin clinical trials on humans and, assuming they go well, a decade before treatment is available to the public. (To avoid heart issues, avoid beer?)