Field of Science

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.

48 comments:

  1. Wow no comments... really?

    This is amazing. We love you.

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  2. Holy shit! This is amazing, only within the last few years have I been researching viruses but Ebola has been by far the scariest that I have researched. I have to admit I am quite envious of the scientists on this team. Thank you for writing this article because otherwise I don't know how I would have heard about this break through, you have to love the media these days.

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  3. so where is this published?

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  4. This is very cool, but part of the problem is delivering the siRNA so soon after infection. Many other anti-virals are effective if given before the symptoms, but few seek treatment before they start feeling sick.

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  5. I guess it's not the issue, because this new medicine will block virus in any stage of proliferation. It's too late only when the damage to the host is already too big to overcome.

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  6. congrats, life changing for those infected!

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  7. "This is very cool, but part of the problem is delivering the siRNA so soon after infection."

    The stage of spread of the virus after 30 minutes of "a dose of Ebola that was 30,000 times greater than the normal fatal dose" would probably be equal to a much longer time of spread from a normal dose.

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  8. In the words of Aristotle: "Four monkeys does not a vaccine make."

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  9. Prof Thomas W Geisbert Corresponding Amy CH Lee, Marjorie Robbins, Joan B Geisbert, Anna N Honko, Vandana Sood, Joshua C Johnson, Susan de Jong, Iran Tavakoli, Adam Judge, Lisa E Hensley, Ian MacLachlan (2010). Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study The Lancet, 375 (9729), 1896-1905 : doi:10.1016/S0140-6736(10)60357-1

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  10. Next time, you may also want to link to the original article that you found so amazing.

    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60357-1/abstract

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  11. 4 monkey's is not a cure. Basic statistics says so.

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  12. I love science!

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  13. Pomax: I did link to the article, which is in The Lancet - see my 2nd paragraph.

    John: agreed, 4 monkeys is not a cure. The same group had already shown the treatment works in guinea pigs, but they wanted to demonstrate it in a primate close to humans. Working with rhesus monkeys is very expensive, though, so I suspect that 4 was all they could manage for this study. And obviously they can't test it on humans.

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  14. You got a few facts wrong there, by the looks of things.
    "Two (66%) of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected."
    Also, saying that they "designed and synthesized RNA sequences that would stick to these 3 proteins like glue" is wrong. They stick to the RNA, not proteins.

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  15. Anon: I was correcting that error while you were posting - it's fixed now. But 4/4 monkeys were indeed cured using a daily treatment regime. In a 2nd experiment, they tried a protocol giving the treatment only on days 1, 3, and 5. This protected 2/3 monkeys, as you say. But when they gave it every day for six days, it protected 4/4 monkeys.

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  16. Wow, that's impressive. The control group may have been small but the fact that the Ebola dose was so potent is very promising.

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  17. Any chance this could work on other viruses like Herpes or HIV?

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  18. AVI Biopharma (ticker: AVII) has supposedly had an effective treatment for Ebola for around seven years: they have had the same amazing success rate in non-human primates. Unfortunately, the company's primary mission seems to be printing more shares instead of making technical progress, and the ebola treatment is still a year away from experimenting in healthy humans (i.e. non-infected) to see if there are any deleterious side-effects.

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  19. There's very little money in a disease cure as compared to a disease treatment . A treatment is like paying a phone bill or magazine subscription. Only in the Ebola case if you cancel it , you die.

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  20. Wow, really pleased to read about this advancement. We need to defeat all viruses like HIV and all the dangers to our species :)

    Good Luck scientists.
    - An Earthling

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  21. can't they test on infected humans?

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  22. Steve,
    Was there was no control group of animals used? In other words, did the researchers assume that the massive dose of virus would be fatal and therefore only tested it in conjunction with the "cure"?

    If that's the case, if you give an overwhelming (an unnatural) dose of virus, could it trigger a massive immune response (like a cytokine storm) which prevents the disease from developing? Thus the "cure" may have done nothing.

    Also, the method and timing of administration of the "cure" may be interesting but the treatment may actually not be curative for people undergoing symptoms but really preventative (ie like a vaccine) for people who know they are infected and yet not undergoing symptoms.

    In other words, the "cure" may be ineffective for people undergoing the clinical symptoms of the disease.

    I think the work is worthy of note and should be discussed further. It may have tremendous promise for Ebola and other diseases.

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  23. Anon: yes, there was a small control group. All control group animals died.

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  24. They were treated 30 minutes after exposure.

    Good luck getting this "cure" to work if you give the initial treatment a day after exposure.

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  25. Not all types of EBOV are pathogenic as stated in the beginning of your article. REBOV is not pathogenic. Please do not jump to conclusions in science writing like others do.

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  26. Is this not a moment like Pasteur curing the little boy of rabies? (I'm referring to the Hollywood version.)

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  27. I truly hope I'm wrong, but I don't see this going anywhere. Drug companies are not in the business of making cures, they're in the business of making suppressants.

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  28. Ebola, it seems, is too lethal and obvious (in its symptoms) to actually be a great cause for concern. Another potential treatment reported lately involves attacking the lipid envelope common to Ebola and many other RNA viruses - such a treatment, if practically possible, may defeat not only Ebola but a host of other, more prevalent, RNA viruses.
    http://www.scientificamerican.com/article.cfm?id=broad-spectrum-anti-viral

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  29. They were treated 30 minutes after exposure, after being giving 30 000 times the lethal dose of the virus...

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  30. It's not super surprising that iRNA should work, so the really clever thing is the delivery method. Now I would assume they just have to work out whether the nanoparticles will kill the patient (human or animal) over a longer time frame, rather than the virus killing the patient quickly.

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  31. siRNA is also being tested as a cure for cancer. About a month ago, they tested an siRNA designed specifically to inject themselves into cancerous cells, which will interrupt the cells' feeding process, and cause them to starve off, and die. They have already done human testing with absolutely (as of yet) 0 side effects. Good to see siRNA being used in more ways.

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  32. Four monkeys is better than anything else so far!

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  33. Yes, but can you protect your monkey from HIV now?

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  34. "Can't they test on infected humans?"

    Really??? You do realize that infected humans live mere days following infection. There's no way they could be identified and treated that quickly. Furthermore, I doubt anyone is going to volunteer to be infected just so the scientists can see what happens!

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  35. Thank you for sharing this!

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  36. Sorry, but I'm going to have to agree that the excitement seems to be a bit premature in this case. Specific RNA-blocking techniques have been attempted in the past, but the real problem is that the vaccines become ineffective after the virus replicates and VP24,35 have been proliferated throughout the body. siRNA has hope as a preventative treatment for those working with the virus (say, in research labs like USAMRIID) or working in close quarters with infected individuals, but this is by no means a "cure".

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  37. Steve, is it true that there were three control animals and one of the control animals survived up until the end of the experiment?

    http://www.drugresearcher.com/Emerging-targets/Progress-towards-Ebola-treatment

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  38. Although it may be a bit "premature" in research to say that it is "THE CURE", specifically to consider the cure GRAS by the FDA, what we can do and what we should do is support these scientists in their research. I believe I read a comment above about Pharm Companies being in the business of suppressants and not in the business of cures you better believe that if this research is in the process of becoming generally recognized as safe they will spend tens of millions so the cure never sees the light of day. Although I may not seem it in this comment I am usually on the pessimistic/realistic side and I strongly believe that all in all we should not only applaud these scientists for their research but support them in any means possible. Their research truly is a milestone for biomedical science.

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  39. Everyone who follows –from time to time- those promising miracles knows that in science you don’t sing aloud “Victory” before the final glory. Interesting and I hope they –and others- follow this line of research etc. But it is too early, too small of a test group –so tiny that you can easily say it’s almost invalid- and so forth.
    Hope the best cure for this and other virus related diseases.

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  40. I don't know why people get off on bringing down the excitement of this. Obviously more study will ensue but siRNA is a sound concept and I hope there is more success! -Rick D

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  41. So... "good" RNA attaches to "bad" RNA and then?, I didn't really got that last part, but this is really interesting.

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  42. Zoe: once the "good" RNA attaches to the viral RNA, it prevents the virus from replicating, so the virus just dies.

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  43. Rabies is an RNA virus,and a much greater problem that Ebola,at least for now.It would be wonderful if Rabies could be treated with this new approach.

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  44. Four monkeys.. really? I'd hate to be the fifth.

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  45. Steven: I think in an earlier post you indicated that there was a small control group and all animals in it died. I think that in the experiment where all the monkeys with treatment lived, there was only One control animal.

    I think this may be an important idea. However, if I'm correct that there was Exactly One control animal, perhaps I am suspicious of the experimental design. Note: the experiment came after the earlier test which showed incomplete protection...Were these results considered statistically significant?

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  46. Anon: yes, the experiment with 4 animals who all lived only had 1 control, who died. They also did another experiments with a different treatment regimens, in which the control animal also died, and the regimen was effective but only cured 2 out of 3 monkeys. In total they had 9 macaques for the experiments.

    Obviously I think the results are significant, but in the formal statistical sense, they are not. It is very costly to do experiments on monkeys, and they would have to use a larger group of animals to get statistical significance. The authors state that they designed this as a proof-of-concept experiment, and that's how it should be interpreted.

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  47. I wonder if this research will be revived in light of the recent Ebola outbreak?

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