Ebola virus disease treatment research

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]

West Africa Ebola Outbreak

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]

A distributed 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.^[9]

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.^[10] A Phase 1 clinical trial involving healthy volunteers was started in early 2014 but suspended by the FDA because of concerns with regards to the safety and possible side effects. However the FDA has approved emergency use to treat patients actually infected with the virus.^[11][12]

• 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 Guinea during December 2014,^[15] with early reports indicating that it has some benefit.^[16]

• BCX4430 is a broad-spectrum antiviral drug developed by BioCryst Pharmaceuticals and currently being researched as a potential treatment for Ebola by USAMRIID.^[17] The drug has been approved to progress to Phase 1 trials, expected late in 2014.^[18] On December 23, it was reported to have positive effects in an animal trial.^[19]

• 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.^[20] A trial commenced during January 2015 in Liberia, but subsequently discontinued due to a lack of suitable subjects.^[21][22]

• 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.^[23][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]

• ZMapp comprises two components from ZMAb, c2G4 and c4G7, combined with c13C6 from another drug, MB-003. Investigators at Public Health Agency of Canada, Kentucky BioProcessing, and the National Institute of Allergy and Infectious Diseases, tested combinations of the antibodies in guinea pigs and then primates to determine the best combination,^[25] which subsequently proved effective in a trial involving rhesus macaque monkeys.^[28][29] The limited supply of the drug was used to treat a small number of individuals infected with the Ebola virus early on in the 2014-5 West Africa outbreak; although some individuals recovered, the outcome is not considered statistically significant.^[30][31] The National Institutes of Health announced on 27 February 2015 the commencement of a randomized controlled trial of ZMapp to be conducted in Liberia and the United States.^[32]

• MIL 77 is a experimental drug manufactured by a Chinese company. The drug was used for the first time in a medical evacuated case in the United Kingdom who survived the virus after receiving this drug. The doctors who used this treatment did confirm it is too early to speculate if this drug was instrumental in her recovery.^[33] The drug was tested in 18 monkeys infected with the deadly virus, and all the primates survived according to the researchers. MIL 77 closely resembles ZMapp.^[34][35]

Existing medicines with possible 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.^[36][37]

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.^[38] 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.^[39] 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.^[40]

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.^[41] 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.^[42]

Interferon therapies have been tried as a form of treatment for EVD, but were found to be ineffective.^[43] Ribavirin is also known to be ineffective against ebolaviruses despite its effectiveness against other viral hemorrhagic fevers such as Lassa fever.^[44]

Lack of available treatment options has spurred research into a number of other possible antivirals targeted against Ebola,^[45][46] including natural products such as scytovirin and griffithsin,^[47][48] as well as synthetic drugs including DZNep,^[49] FGI-103, FGI-104, FGI-106, dUY11 and LJ-001,^[50] and other newer agents.^{[51][52][53][54][55][56][57]}

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.^[58]

The Russian Academy of Sciences has developed an anti-viral drug called Triazavirin, which is said to be effective against influenza and Lassa fever as well as Ebola and Marburg filoviruses, and might be available for clinical trials in 2015. ^[59][60][61]

The compound Tetrandrine derived from a Chinese medicinal herb has been shown in vitro to inhibit release of Ebola virus from the macropinosomes in which they enter the host cells, thereby trapping them and preventing replication. The compound also showed therapeutic efficacy against Ebola virus in preliminary studies on mice.^[62][63]

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][64] and have issued an interim guideline for this therapy.^[65] The method was used on a small cohort of 8 patients during a 1996 outbreak in the Congo with results which were promising but not conclusive.^[66] The first clinical trial of this therapy, involving 70 patients, started at the ELWA 2 treatment Centre in Liberia during December 2014 with funding from the Gates Foundation in coordination with national health authorities and WHO. Further trials are planned in Guinea and Sierra Leone.^[67]

Hemopurifier

The Hemopurifier is a single-use disposable cartridge designed for use with dialysis machines and other blood circulatory pumps. It functions to selectively remove harmful substances from the blood, giving a potential method of addressing diseases.

During October 2014 the Hemopurifier was used as an adjunct in the treatment of a patient who was suffering from Ebola, who subsequently recovered.^[68] The FDA has subsequently approved the device for testing in up to 20 infected Ebola cases in the United States.^[69]

See also

• Ebola vaccine
• Ebola virus epidemic in West Africa

References

Topics of most severely affected countries Guinea topics History Regional history Songhai Empire Imamate of Futa Jallon Wassoulou Empire African slave trade French West Africa Rivières du Sud French Guinea Guinea-Bissau War of Independence Portuguese invasion Camp Boiro 2007 protests 2008 military unrest 2008 coup d'état 2009 protests 2014 Ebola virus epidemic Geography Biosphere reserves Cities Ecoregions Mountains Protected areas Rivers Wildlife Politics Administrative divisions Cabinet Elections Foreign relations Human rights Military Parliament Political parties President Prime Minister Economy Agriculture Central bank Energy Franc (currency) Telecommunications Trade unions Transport Society Demographics Education Ethnic groups Health Languages Religion Culture Anthem Cinema Cuisine Coat of arms Flag Music Polygamy Sports Outline Index Category Portal WikiProject Liberia topics History Colonization (1821–1847) Americo-Liberian rule (1847–1980) Samuel Doe era (1980-1989) First Liberian Civil War (1989–1997) Second Liberian Civil War (1999–2003) 2014 Ebola virus epidemic Geography Cities Environmental issues Forests Islands Mountains Rivers Wildlife Politics Administrative divisions Constitution Elections Cabinet Foreign relations Government ministries Human rights Judiciary Law enforcement Parliament Political parties President Military Economy Agriculture Central bank Communications Dollar (currency) Energy Tourism Transportation Society Corruption Crime Demographics Education Ethnic groups Health Languages Public holidays Religion Women Culture Coat of arms Cuisine Flag Media Music Polygamy Sport Outline Index Category Portal WikiProject Mali topics History Ghana Empire Pre-Imperial Mali Mali Empire Songhai Empire Bamana Empire Kénédougou Kingdom Kaarta Massina Empire Toucouleur Empire Wassoulou Empire French Sudan Mali Federation 2012 Tuareg rebellion 2012 coup Northern Mali conflict Ebola disease event Geography Cercles Cities Communes Environmental issues Mountains National parks Regions Rivers Wildlife Politics Constitution Elections Foreign relations Human rights Law enforcement Military National Assembly Political parties President Prime Minister Economy Foreign aid Telecommunications Tourism Transport Society Demographics Ethnic groups Education Health Languages Religion Slavery Women Culture Cuisine Films Flag Literature Media Music Polygamy Public holidays Outline Index Category Portal WikiProject Nigeria topics History Kingdoms Empires Nri Oyo Benin Fulani Aro Kanem-Bornu Timeline Northern Nigeria Southern Nigeria Civil War Islamist insurgency Niger Delta conflict 2014 Ebola outbreak Geography Adamawa Plateau Cities Ecoregions Environmental issues Islands Jos Plateau Mountains National parks Niger Delta Rivers Niger Wildlife Politics Administrative divisions Cabinet Constitution Elections Federal Executive Council Foreign relations Human rights Law enforcement LGBT history Military National Assembly House of Representatives Senate Political parties PDP ANPP ACN President Vice-President Supreme Court Economy Agriculture Central Bank Economic history Energy Mining Naira (currency) Petroleum Stock Exchange Telecommunications Tourism Transport Society Corruption Demographics Education Ethnic groups MASSOB MOSOP Oodua Peoples Congress Health Languages Organized crime Poverty Rankings Refugees Water supply and sanitation Culture Anthem Cinema Coat of arms Cuisine Flag List of Nigerians Literature Media Music Public holidays Religion Smoking Sport Outline Index Category Portal WikiProject Sierra Leone topics History Atlantic slave trade (1600-1787) British colony (1800-1961) Early independence (1961–1978) Civil War (1991–2002) 2002 to present 2014 Ebola virus epidemic Geography Cities and towns Climate Protected areas Upper Guinean forests Water supply Wildlife Politics Administrative divisions Cabinet Elections Foreign relations Human rights Law enforcement Military Parliament Political parties President Special Court Supreme Court Economy Agriculture Banking Central bank Leone (currency) Mining Telecommunications Tourism Transport Society Demographics Education Ethnic groups Health Languages Religion Women Culture Anthem Art Coat of arms Cuisine Flag Media Music Polygamy Sports Outline Index Book Category Portal WikiProject