GENE therapy could soon be used to treat heart failure. Initial results suggest the treatment is both effective and long-lasting.
When the heart can鈥檛 pump enough blood, fluids collect in the body鈥檚 tissues, causing swelling, shortness of breath and fatigue. In the worst cases, the only treatment is a new heart, but many patients die waiting for a donor.
While heart failure has many causes, Kenneth Chien at the University of California, San Diego, and his team have shown that a common feature is an overactive protein called phospholamban or PLN. In healthy people it helps regulate the activity of heart muscle cells, but in people with heart failure it seems to be too effective and prevents cells both from contracting strongly and relaxing completely.
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To see if blocking PLN could help, Chien鈥檚 team created a virus carrying a gene for a mutated PLN protein that inhibits the normal protein. When they injected this into a breed of hamster that suffers from progressive heart failure it had a dramatic effect. The treatment doubled the capacity of the animals鈥� hearts to contract and relax, and they were able to sustain blood pressure about a third higher than untreated animals (Nature Medicine, DOI:10.1038/nm739). The benefits were still apparent seven months later.
鈥淚t鈥檚 fabulous work for a number of reasons,鈥� says Elizabeth Nabel, a cardiologist at the National Institutes of Health near Washington DC. For one thing, she says, the treatment doesn鈥檛 appear to damage the heart as some drug treatments that cause long-term hyperactivation of cardiac muscle do.
Chien鈥檚 team already has unpublished data showing the treatment works in mice and rats with heart failure. They now plan to test the technique in pigs. If it works for them, Chien says the therapy will be tested on patients whose age or health makes them poor candidates for transplants. 鈥淲e aren鈥檛 cowboy cardiologists eager to get this into any patient,鈥� he says. 鈥淲e鈥檙e going to err on the side of caution.鈥�