Hacking the Immune System to Prevent Damage after a Heart Attack
Microparticles that block the body’s immune response to damaged tissue could help prevent further harm.
There are no therapies that prevent tissue damage due to the inflammatory response after a heart attack.
Using tiny biodegradable particles to disrupt the body’s normal immune response after a heart attack could help save patients from tissue damage and certain long-term health problems that often follow. Researchers have shown that injecting such particles into mice within 24 hours of a heart attack not only significantly reduces tissue damage, but also results in those mice having stronger cardiac function 30 days later. The inventors of the new technology now plan to pursue human trials.
Much of the tissue damage that results from a heart attack is the result of inflammation, the body’s natural response to harmful stimuli such as damaged muscle. But in the case of a heart attack, these immune cells do more harm than good, explains Daniel Getts, inventor of the new therapy and chief scientific officer of Cour Pharmaceutical Development. The system’s weaponry is “fairly generic,” he says. While the toxic compounds that the immune cells secrete can be beneficial in defending the body against an infection, they also cause tissue damage. This phenomenon occurs not only after heart attacks, but also in a range of other diseases, including West Nile Virus, inflammatory bowel disease, and multiple sclerosis.
The 500-nanometer particles must be negatively charged, and can be made of several different materials, including the one used for biodegradable sutures. The new research suggests that once the particles are in the bloodstream, the negative charge attracts a specific receptor on the surface of inflammatory monocytes. The particles bind to that receptor and divert the immune cells away from the heart and toward the spleen, where they die.
Preventing these cells from reaching the heart allows the damaged muscle to regenerate “along more regulated processes,” says Getts. Should the therapy translate to humans, he says, it has the potential to substantially reduce the long-term health drawbacks that some heart attack patients experience, including shortness of breath and limited ability to exercise.
The goal is to begin human tests by early next year. The company hopes the relatively simple mechanism of the therapy, and the fact that the material the particles are made of, polyglycolic acid, is already approved by the U.S. Food and Drug Administration, will speed the development process.
But “there is still some homework to do,” in particular the teasing out of any potential side effects the microparticles might produce, says Matthias Nahrendorf, a professor of systems biology at Harvard. For example, the particles may activate the immune system in some yet-unknown way, he says. In addition, it will be important to determine how to administer the therapy so that it doesn’t compromise these cells’ ability to help in healing, and to defend the body against infection and other foreign invaders, says Nahrendorf.