A breakthrough cure for Ebola

Ebola is one of the nastiest, most frightening viruses known to man. Its victims suffer fevers, muscle weakness, and other symptoms that progress to severe bleeding, both internal and external, that eventually causes them to bleed to death. All known strains of Ebola virus have very high mortality rates, ranging from 25% to 90%, and there is no cure. Ebola virus was the subject of a dramatic and frightening 1995 disaster movie, Outbreak, starring Dustin Hoffman, Rene Russo, and Morgan Freeman.

Last week, in what may be the biggest medical breakthrough of its kind in years, a group of scientists published results in The Lancet describing a completely new type of anti-viral treatment that appears to cure Ebola. They report a 100% success rate, although admittedly the test group was very small, just 4 rhesus monkeys.

This is a breakthrough not only because it may give us a cure for an uncurable, incredibly nasty virus, but also because the same method might work for other viruses, and because we have woefully few effective antiviral treatments. We can treat bacterial infections with antibiotics, but for most viruses, we have either a vaccine or nothing. And a vaccine, wonderful as it is, doesn’t help you after you’re already infected.

The scientists, led by Thomas Geisbert at Boston University, used a relatively new genomics technique called RNA interference to defeat the virus. Here’s how it works. First, a little background: the Ebola virus is made of RNA, just like the influenza virus. And just like influenza, Ebola has very few genes - only 8. One of its genes, called L protein, is responsible for copying the virus itself. Two others, called VP24 and VP35, interfere with the human immune response, making it difficult for our immune system to defeat the virus.

Geisbert and his colleagues (including scientists from Tekmira Pharmaceuticals and USAMRIID) designed and synthesized RNA sequences that would stick to these 3 genes like glue. How did they do that? We know the Ebola genome’s sequence – it was sequenced way back in 1993. And we know that RNA sticks to itself using the same rules that DNA uses. This knowledge allowed Geisbert and colleagues to design a total of 10 pieces of RNA (called “small interfering RNA” or siRNA) that they knew would stick to the 3 Ebola genes. They also took care to make sure that their sticky RNA would not stick to any human genes, which might be harmful. They packaged these RNAs for delivery by inserting them into nanoparticles that were only 81-85 nanometers across.

In the key experiment, the scientists infected rhesus monkeys with a dose of Ebola that was 30,000 times greater than the normal fatal dose. They injected the siRNA treatments 30 minutes later, and again each day for 6 days. All the monkeys survived with no long-term effects.

When I read this story in The Lancet, my first reaction was: wow. A brand-new antiviral treatment, and against Ebola? In a commentary in The Lancet, Heinz Feldmann wrote that we are “in desperate need of approved countermeasures against Ebola-virus infections,” and called the new study a “milestone.” That’s putting it mildly.

Somehow, except for the UK Daily Mail, the major media outlets seem to have entirely missed this story, which I think is by far the biggest medical story of the week, if not the year. Ebola virus doesn’t get much attention (notwithstanding the 1995 movie about it), primarily because it occurs in central Africa. But air travel has made our world much smaller, and even a relatively isolated virus could easily get out of control.

There’s still a much work needed to turn the new Ebola treatment into an approved drug, but the prospect of a cure is suddenly very real, and the techniques used to create it are truly remarkable.