Researchers from QIMR Berghofer Medical Research Institute and Cambridge University in the UK have discovered a way to potentially allow the heart to regenerate itself, a finding that could in the future help millions of people worldwide suffering from heart disease.
The researchers had been working on trying to turn off a gene that allows cancers to spread and surprisingly found by making the gene overactive in the hearts of mice, it triggered the heart cells to regenerate.
Lead researcher, Dr Catherine Wilson, from the University of Cambridge’s Department of Pharmacology said adult hearts usually did not repair themselves once damaged, so harnessing the power of the Myc cancer gene represented major progress towards the first curative treatment for heart disease.
“This is really exciting because scientists have been trying to make heart cells proliferate for a long time. None of the current heart disease treatments is able to reverse degeneration of the heart tissue – they only slow progression of the disease. Now we’ve found a way to do it in a mouse model,” Dr Wilson said.
Cancer develops when cells start to replicate themselves uncontrollably, and the Myc gene plays a key role in the process.
Myc is known to be overactive in most cancers, and has been a high priority target gene for cancer researchers. Much recent research has focused on trying to control Myc as a means of cancer therapy.
Study first author and senior research officer in the Gordon and Jessie Gilmour Leukaemia Research Group at QIMR Berghofer, Dr Megan Bywater, said they were working on the Myc gene in mice when they saw its cancerous effects in some organs, including the liver and lungs, but not in the heart.
“We found that Myc-driven activity in heart muscle cells was critically dependent on the level of another protein called Cyclin T1, which is made by a gene called Ccnt1, within the cells. When the Ccnt1 and Myc genes were expressed together, the heart switched into a regenerative state and its cells started to replicate,” Dr Bywater said.
“When those two genes were overexpressed together in the heart muscle cells of adult mice we saw extensive cell replication, leading to a large increase in the number of heart muscle cells.”
Heart failure affects about 23 million people worldwide each year, and there is currently no cure. After a heart attack, an adult human heart can lose up to one billion heart muscle cells.
Unlike many other organs in the body, the adult heart does not regenerate itself, so the cells are never replaced. The cell loss reduces the strength of the heart and causes scar formation, heart failure and ultimately death.
Using a next generation sequencing technology called ChIP, the researchers were able to watch the action of Myc in the heart cells. Myc produces a protein that binds to the DNA in specific cells and activates gene expression. But despite the protein binding successfully, the heart cells did not start replicating themselves because the protein could not activate gene expression. Another protein vital to gene expression, Cyclin T1, was deficient in the heart, but the researchers found by adding it to the cells with the overactive Myc the cells started proliferating.
“None of the current treatment options can reverse the degeneration of heart tissue. The inability of the heart to regenerate itself is a significant unmet clinical need,” Dr Wilson said.
“We found that even when Myc is switched on in a heart, the other tools aren’t there to make it work, which may be one of the reasons heart cancer is so extremely rare. Now we know what’s missing, we can add it and make the cells replicate.”
Dr Wilson and Associate Professor James Hudson from QIMR Berghofer’s Cardiac Bioengineering group are continuing to collaborate on translating these findings into a cardiac regenerative therapy.
“We want to use short-term, switchable technologies to turn on Myc and Cyclin T1 in the heart. That way we won’t leave any genetic footprint that might inadvertently lead to cancer formation,” Dr Wilson said.
This research was funded by Cancer Research UK.