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Rewriting Life

A Cure for MERS (in Mice)

Genetically engineered mice treated for Middle East respiratory syndrome are disease-free, but it’s not yet clear if it will work for humans.

Because diseases like MERS are rare, there’s less of an incentive to develop drugs to treat them.

A New York company has figured out how to give mice the virus that causes Middle East respiratory syndrome (MERS), and also how to prevent the disease and effectively treat the infected mice.

The virus has sickened more than 1,000 people and killed more than 400 in and around Saudi Arabia, and has recently spread to South Korea. But because the disease has only been recognized since 2012 and remains relatively rare, there has been little interest in developing a drug to treat the condition. 

The company, Regeneron Pharmaceuticals of Tarrytown, New York, says its process of genetic engineering and antibody development shortens the usual drug development process, making it more economically viable. In infections where the body cannot produce its own antibodies fast enough, antibody-based treatments can rev up the immune system to target and neutralize dangerous pathogens.

The treatment still needs to be proved in humans, but the company says its antibody discovery the approach has already worked in Ebola, and can be used treat other emerging viral diseases as well.

“Instead of just trying to invent new drugs, we also invent new technologies that enable us to make new drugs more reliably and more rapidly,” says Neil Stahl, Regeneron’s executive vice president of research and development. The MERS results were published Monday in the Proceedings of the National Academy of Sciences.

To develop its treatment, company scientists screened about 1,000 different antibodies that bind to the virus that causes MERS, known as MERS-CoV. They isolated the ones that looked the most promising, Stahl says. The company then showed that its antibodies could block the disease if given to mice either the day before or after infection with MERS. This process of antibody development usually takes about 18 months, Stahl said, but his company accomplished it in under six. 

One of the challenges of working with diseases like MERS is that the virus doesn’t affect mice the way it does people. So the company genetically engineered a mouse to have human immune receptors and therefore become vulnerable to MERS. This mouse is now a reliable model for the human form of the disease, the paper showed, and can be used for other research into it.

The company used a similar process to develop antibodies against Ebola that are being tested in animals, Stahl says.

Stephen Morse, a professor of epidemiology at Columbia University’s Mailman School of Public Health, says he’s happy to see the company turning its attention to MERS, which has no treatment other than addressing patient symptoms. Morse says he is impressed that the company could develop the mouse model of the disease, which will help researchers better understand the viral illness and develop treatments.

However, the study didn’t convince him that the antibodies will help patients with more advanced disease, like the South Korean traveler who carried the virus home from the Middle East and directly or indirectly infected 180 others. Morse says he’d like to see the drug tested in later stages of the disease to be sure of its effectiveness.

Regeneron’s results suggest that the antibodies will be safe to use in people, Stahl says. “Based on everything we know, we wouldn’t expect them to interact or bind to anything in a person, so we think they’re exceedingly safe.”

But, Morse cautions, there’s always a difference between how a lab animal reacts to a treatment and how that treatment will work in the real world. 

Another company’s experimental Ebola treatment, TKM-Ebola, which looked extremely effective when tested on monkeys, was recently discontinued in clinical trials in West Africa after it failed to help patients. (A promising antibody-based drug, ZMapp, is still being tested in people.)

Morse says he hopes Regeneron’s MERS treatment will prove more effective. “There’s no reason why it shouldn’t be successful, but it’s very hard to predict until it’s actually in clinical trials [in people].”

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