A dose of CRISPR-edited heart cells has boosted the survival of rats with chronic heart failure and increased how much they exercised. Tests of the technique in humans could happen within a few years.
Chronic heart failure, where the heart fails to pump blood effectively around the body, is a leading cause of death worldwide. For most people, this long-term condition 鈥� involving slow, weak heart contractions 鈥� can鈥檛 be cured, but its symptoms are commonly treated using drugs that widen blood vessels and reduce blood pressure.
Now, at the University of Washington in Seattle and his colleagues have modified human heart cells using CRISPR gene editing to produce high levels of a molecule called dATP, which helps heart cells contract faster and stronger.
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To test the cells, the researchers turned to rats that had surgically induced heart injury to mimic chronic heart failure. They injected 10 million gene-edited human heart cells into the hearts of 16 rats and 10 million non-edited heart cells into the hearts of 14 rats, and gave 10 rats an injection containing no cells.
After three months, all rats treated with the gene-edited heart cells were still alive and about 90 per cent of rats treated with unedited heart cells had survived, but just 60 per cent of rats that received no heart cells survived.
鈥淭he gene-edited cells tackle two root causes of heart failure by, firstly, partially replacing dead heart cells at the site of injury and, secondly, by boosting contractions in surviving heart cells across the heart by manufacturing dATP that then diffuses across the heart,鈥� says Murry.
Chronic heart failure often leads to fatigue and a reduced capacity for exercise, so the researchers also measured how far rats travelled on an exercise wheel in a 12-hour period at the end of the experiment. Rats treated with the gene-edited heart cells ran nearly twice as far as those given unedited heart cells, and roughly three times as far as the control group of rats.
鈥淲hile this study is still in its early stages, it provides proof of concept for a new direction in regenerative medicine,鈥� says at Stanford University in California. 鈥淭he rat model offers valuable insight into the effectiveness of the treatment, but further research is necessary to determine if these findings can be replicated in large animal studies and humans.鈥�
Potential problems include rejection of the cells by the immune system and the cells forming tumours, says Wu.
鈥淭he rats we used were immunodeficient, so we effectively took the immune system out of the equation in this study,鈥� says Murry. But in the clinic, drugs that suppress the immune system could be used to reduce immune rejection, he says.
The gene-edited cells should 鈥渓ast for the lifetime of the animal or the patient鈥�, says Murry, and he thinks trials in humans to assess whether the technique works and if there are safety problems could potentially start in 2025.
bioRxiv
