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→Existing medicines with anti-Ebola activity: 53 existing drugs reference. The list includes some of the drugs which are mentioned in the next 2 paras.
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==Existing medicines with anti-Ebola activity==
==Existing medicines with anti-Ebola activity==
A study led by researchers at the [[Icahn School of Medicine]] and the [[National Institutes of Health]] in December 2014 identified 53 existing drugs that may be effective at preventing the Ebola virus from entering human cells. The research effort will continue in order to investigate the safety and potential effectiveness of these compounds.<ref>{{cite journal|last1=Kouznetsova|first1=Jennifer|last2=Sun|first2=Wei|last3=Martínez-Romero|first3=Carles|last4=Tawa|first4=Gregory|last5=Shinn|first5=Paul|last6=Chen|first6=Catherine Z|last7=Schimmer|first7=Aaron|last8=Sanderson|first8=Philip|last9=McKew|first9=John C|last10=Zheng|first10=Wei|last11=García-Sastre|first11=Adolfo|title=Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs|journal=Emerging Microbes & Infections|date=17 December 2014|volume=3|issue=12|pages=e84|doi=doi:10.1038/emi.2014.88}}</ref><ref>{{cite web|title=53 Ebola-blocking drugs identified among existing medications|url=http://www.medicalnewstoday.com/articles/287225.php|accessdate=7 January 2015}}</ref>

Two [[selective estrogen receptor modulator]]s usually used to treat infertility and breast cancer ([[clomiphene]] and [[toremifene]]) have been found to inhibit the progress of Ebola virus ''in vitro'' as well as in infected mice. Ninety percent of the mice treated with clomiphene and 50 percent of those treated with toremifene survived the tests.<ref name="Johansen_2013">{{cite journal|author= Johansen LM, Brannan JM, Delos SE, Shoemaker CJ, Stossel A, Lear C, Hoffstrom BG, Dewald LE, Schornberg KL, Scully C, Lehár J, Hensley LE, White JM, Olinger GG|title=FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection|journal=Sci Transl Med|volume=5|issue=190|pages=190ra79|date=June 2013|pmid=23785035|pmc=3955358|doi= 10.1126/scitranslmed.3005471| laysummary=http://www.healthline.com/health-news/tech-breast-cancer-drugs-fight-ebola-virus-infection-062013|laysource=Healthline Networks, Inc.|last2=Brannan|last3=Delos|last4=Shoemaker|last5=Stossel|last6=Lear|last7=Hoffstrom|last8=Dewald|last9=Schornberg|last10=Scully|last11=Lehár|last12=Hensley|last13=White|last14=Olinger}}</ref> The study authors conclude that given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.
Two [[selective estrogen receptor modulator]]s usually used to treat infertility and breast cancer ([[clomiphene]] and [[toremifene]]) have been found to inhibit the progress of Ebola virus ''in vitro'' as well as in infected mice. Ninety percent of the mice treated with clomiphene and 50 percent of those treated with toremifene survived the tests.<ref name="Johansen_2013">{{cite journal|author= Johansen LM, Brannan JM, Delos SE, Shoemaker CJ, Stossel A, Lear C, Hoffstrom BG, Dewald LE, Schornberg KL, Scully C, Lehár J, Hensley LE, White JM, Olinger GG|title=FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection|journal=Sci Transl Med|volume=5|issue=190|pages=190ra79|date=June 2013|pmid=23785035|pmc=3955358|doi= 10.1126/scitranslmed.3005471| laysummary=http://www.healthline.com/health-news/tech-breast-cancer-drugs-fight-ebola-virus-infection-062013|laysource=Healthline Networks, Inc.|last2=Brannan|last3=Delos|last4=Shoemaker|last5=Stossel|last6=Lear|last7=Hoffstrom|last8=Dewald|last9=Schornberg|last10=Scully|last11=Lehár|last12=Hensley|last13=White|last14=Olinger}}</ref> The study authors conclude that given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.


Revision as of 20:21, 7 January 2015

This article is about current experimental treatments to fight the Ebola virus. For the ongoing outbreak in Africa, see Ebola virus epidemic in West Africa.
Ebola virus virion

Ebola virus disease, or simply Ebola, is a disease of humans and other primates caused by ebolaviruses. There is no cure or specific treatment that is currently approved.[1] Treatment is primarily supportive in nature.[2]

In March 2014, the World Health Organization (WHO) reported a major Ebola outbreak in Guinea, a western African nation.[3] The disease then rapidly spread to the neighboring countries of Liberia and Sierra Leone. It is the largest Ebola outbreak ever documented, and the first recorded in the region.[3]

The director of the US National Institute of Allergy and Infectious Diseases has stated that the scientific community is still in the early stages of understanding how infection with the Ebola virus can be treated and prevented.[4] The unavailability of treatments in the most-affected regions has spurred controversy, with some calling for experimental drugs to be made more widely available in Africa on a humanitarian basis, and others warning that making unproven drugs widely available would be unethical, especially in light of past experimentation conducted in developing countries by Western drug companies.[5][6] As a result of the controversy, on 12 August an expert panel of the WHO endorsed the use of interventions with as-yet-unknown effects for both treatment and prevention of Ebola, and also said that deciding which treatments should be used and how to distribute them equitably were matters that needed further discussion.[7]

Conventional trials to study efficacy by exposure of humans to the pathogen are obviously not feasible in this case. For such situations, the FDA has established the “Animal Efficacy Rule” allowing limited licensure to be approved on the basis of animal model studies that replicate human disease, combined with evidence of safety. A number of experimental treatments are being considered for use in the context of this outbreak, and are currently or will soon undergo clinical trials.[8]

Experimental treatments being researched

A researcher working with the Ebola virus while wearing a BSL-4 positive pressure suit to avoid infection
  • TKM-Ebola, an RNA interference drug.[9] A Phase 1 clinical trial involving healthy volunteers was started in early 2014 but suspended because of concern over side effects; however the FDA has approved emergency use to treat patients actually infected with the virus.[10][11] On December 4, it was reported that TKM-Ebola is "on a partial clinical hold because the U.S. Food and Drug Administration"[12] has concerns with regards to the safety data it has put forth.
  • Favipiravir (Avigan), is approved in Japan for use against influenza, which appears to be useful in a mouse model of Ebola disease.[13][14] A clinical trial started in Guéckédou, Guinea during December 2014.[15]
  • Brincidofovir, another antiviral drug, has been granted an emergency FDA approval as an investigational new drug for the treatment of Ebola after it was found to be effective against Ebola virus in in vitro tests.[19] A trial commenced during January 2015 in Liberia.[20]
  • JK-05 is an antiviral drug developed by the Chinese company Sihuan Pharmaceutical along with the Chinese Academy of Military Medical Sciences. In tests on mice, JK-05 shows efficacy against a range of viruses, including Ebola. It is claimed to have a simple molecular structure, which should be readily amenable to synthesis scale-up for mass production. The drug has been given preliminary approval by the Chinese authorities to be available for Chinese health workers involved in combating the outbreak, and Sihuan are preparing to conduct clinical trials in West Africa.[21][22]
  • Interferon therapies have been tried as a form of treatment for EVD, but were found to be ineffective.[23] Ribavirin is also known to be ineffective against ebolaviruses despite its effectiveness against other viral hemorrhagic fevers such as Lassa fever.[24]
  • ZMAb is composed of equal parts of three monoclonal antibodies directed against the envelope glycoproteins of the Ebola virus: m1H3, m2G4 and m4G7.[25][26] A study published in November 2013 found that EBOV-infected macaque monkeys survived after being treated with ZMab within 24 hours of infection. The authors concluded that post-exposure treatment resulted in a robust immune response, with good protection for up to 10 weeks and some protection at 13 weeks.[27]
  • Researchers in Thailand claim to have developed an antibody-based treatment for Ebola using synthesized fragments of the virus. It has not been tested against Ebola itself. Scientists from the WHO and NIH have offered to test the treatment against live Ebola virus, but there is still a great deal of development needed before human trials.[33]

Existing medicines with anti-Ebola activity

A study led by researchers at the Icahn School of Medicine and the National Institutes of Health in December 2014 identified 53 existing drugs that may be effective at preventing the Ebola virus from entering human cells. The research effort will continue in order to investigate the safety and potential effectiveness of these compounds.[47][48]

Two selective estrogen receptor modulators usually used to treat infertility and breast cancer (clomiphene and toremifene) have been found to inhibit the progress of Ebola virus in vitro as well as in infected mice. Ninety percent of the mice treated with clomiphene and 50 percent of those treated with toremifene survived the tests.[49] The study authors conclude that given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.

A 2014 study found that three ion channel blockers used in the treatment of irregular heart rhythms, amiodarone, dronedarone and verapamil, block the entry of Ebola virus into cells in vitro.[50] Unapproved use of amiodarone in human Ebola patients at one clinic in Sierra Leone, was however described as "reckless" and may have actually contributed to an increased likelihood of death.[51]

A distributing computing project, Outsmart Ebola Together, has been launched by World Community Grid in collaboration with the Scripps Research Institute to help find chemical compounds to fight the disease. It uses the idle processing capacity of volunteers' computers and tablets. [52]

Lamivudine, usually used to treat HIV/AIDS, was reported by a doctor in Liberia to have been used successfully to treat 13 out of 15 Ebola-infected patients.[53] Dr Benjamin Neuman, a virologist at the University of Reading, said he would need to see the results of a larger test before drawing conclusions about any treatment.[54]

Blood products

The WHO has stated that transfusion of whole blood or purified serum from Ebola survivors is the therapy with the greatest potential to be implemented immediately, although the efficacy of this approach has not been proven.[30][55] In September 2014, WHO issued an interim guideline for this therapy.[56] The blood serum from those who have survived an infection is currently being studied to see if it is an effective treatment.[57] During a meeting arranged by WHO, this research was deemed to be a top priority.[57] Seven of eight people with Ebola survived after receiving a transfusion of blood donated by individuals who had previously survived the infection in a 1999 outbreak in the Democratic Republic of the Congo.[2][58] This treatment, however, was started late in the disease meaning they may have already been recovering on their own and the rest of their care was better than usual.[2] Thus this potential treatment remains controversial.[59] Intravenous antibodies appear to be protective in nonhuman primates who have been exposed to large doses of Ebola.[60] The WHO has approved the use of convalescent serum and whole blood products to treat people with Ebola.[61]

Dr. Peter Piot, who co-discovered Ebola in 1976 in Africa, said that the therapy was the only one available at the time of its discovery, and it carried a number of risks.[62] Twenty years later, when the method was again used during a 1996 outbreak in the Congo, the results were promising, as only one out of eight patients died.[63] Disease specialist Dr. Mark Gendreau speculates that it may hold the most hope for infected patients as a treatment,[64] whereas Dr. Paul Skolnik, director of the Ebola Task Force at the University of Connecticut, notes that such antibodies may also potentially be used to prevent Ebola infections.[65] In Israel, virologist Leslie Lobel has been working, for over a decade, on developing a vaccine or treatment using the antibody serum from African Ebola survivors, who he calls "those who have the gold in their blood that enabled them to survive this serious disease."[62][66]

Hemopurifier

Scientists are evaluating the possibilities of the Hemopurifier filtering Ebola virus out of the blood.[67]

On 2 January 2015 the FDA approved the use of Aethlon's Hemopurifier. The device is similar to kidney dialysis and purifies the blood by filtering out viruses and toxins. The bio-filtration device consists of "dialysis" of 6 to 8 hours a day until the viral load drops to less than 1,000 copies/ml. It has been used before in Germany on a severely ill medivac Ebola case where the viral load dropped from 400,000 copies/ml to 1,000 copies/ml after 6.5 hours of therapy. This device is being used in India on hepatitis C patients to decrease the viral load of the disease. Aethlon announced the FDA's approval allowing a study to be conducted in up to 20 infected Ebola cases in the United States.[68]

The first Ebola patient to receive this treatment was a Ugandan medically evacuated from Sierra Leone to Germany. During his 6.5 hour treatment his viral load dropped from 400,000 copies/ml blood to about 1,000 copies/ml. The filter was sent to a biosafety level 4 laboratory at the University of Marburg where it was determined that the filter trapped 242 million copies of the Ebola virus.[67]

See also

References

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