Ebola virus disease treatment research

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. Treatment is primarily supportive in nature.

Context

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

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. 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. 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.

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.

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.

Experimental treatments being researched

A researcher working with the Ebola virus while wearing a BSL-4 positive pressure suit to avoid infection

• ZMapp is a combination of three chimeric antibodies effective in Ebola-infected monkeys. 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. A Phase 1/2 trial started in Liberia and the United States on 27 February 2015.
• Favipiravir (Avigan) is a broad-spectrum antiviral drug, which appears to be useful in a mouse model of Ebola disease. A Phase 2 clinical trial started in Guinea during December 2014, with early reports indicating that it has some benefit.

• BCX4430 is a broad-spectrum nucleoside analog antiviral drug developed by BioCryst Pharmaceuticals. A Phase 1 trial started in December 2014. The drug was effective in Ebola-infected monkeys.
• Monoclonal antibodies derived from blood samples of infected patients, under development by Theraclone Sciences in Seattle.
• 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. A Phase 2 trial started during January 2015 in Liberia, but was subsequently discontinued due to a lack of suitable subjects.
• TKM-Ebola is an RNA interference drug candidate; a Phase II trial started on 11 March 2015 and stopped enrolling new subjects on 19 June 2015 after it appeared not to work; statistical analysis was ongoing at the time.
• AVI-7537 is an antiviral drug developed by Sarepta Therapeutics, which was effective in Ebola-infected monkeys. A Phase 1 trial May 2010 to November 2011 showed that the drug was safe in healthy adults; however, a later Phase 1 trial was withdrawn due to funding constraints.
• JK-05 is an antiviral drug developed by Sihuan Pharmaceutical along with 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.
• MIL 77 is an experimental drug 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. 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.

Blood products

The WHO has stated that transfusion of whole blood or purified serum from Ebola survivors has the greatest potential to be implemented immediately, and has issued an interim guideline for this therapy. A study in Sierra Leone started in November 2014, and preliminary results show an 80 percent survival rate. Trials in Liberia and Guinea started in January 2015, with funding from the Gates Foundation. Blood transfusions were also used in a 1995 outbreak in the Democratic Republic of the Congo, and 7 out of 8 patients survived.

Existing drugs without anti-Ebola activity

Ribavirin is also known to be ineffective against ebolaviruses despite its effectiveness against other viral hemorrhagic fevers such as Lassa fever.

Interferon therapies have been tried as a form of treatment for EVD, but were found to be ineffective.

Potential diagnostic tests

One issue which hinders control of Ebola is that diagnostic tests which are currently available require specialised equipment and highly trained personnel. Since there are few suitable testing centres in West Africa, this leads to delay in diagnosis. In December, a conference in Geneva will aim to work out which diagnostic tools could identify Ebola reliably and more quickly. The meeting, convened by the WHO and the non-profit Foundation for Innovative New Diagnostics, seeks to identify tests that can be used by untrained staff, do not require electricity or can run on batteries or solar power and use reagents that can withstand temperatures of 40 °C.

As of February  2015 a number of diagnostic tests are under trial:

• Diagnostics-in-a-Suitcase, based on Recombinase Polymerase Amplification (RPA). The new equipment, about the size of a laptop and solar-powered, allows testing to be done in remote areas; testing commenced in Guinea during January 2015.
• In December 2014, the FDA approved LightMix (R) Ebola Zaire rRT-PCR Test for emergency use on patients with symptoms of Ebola.
• Massachusetts Institute of Technology has developed a 10-minute Ebola test using Matrix Multiplexed Diagnostic (MMDx) technology. This still has to complete testing to gain FDA approval.
• Corgenix Medical Corp announced on 26 February that health regulators had approved its rapid Ebola test for emergency use. The ReEBOV Antigen Rapid Test involves putting a drop of blood on a paper strip and waiting for at least 15 minutes for a reaction.
• On 29 March, a new rapid Ebola virus diagnostic kit/test was developed by British military scientists and NHS in Sierra Leone.

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. The FDA has subsequently approved the device for testing in up to 20 infected Ebola cases in the United States.

See also

• Ebola vaccine
• Ebola virus epidemic in West Africa