The Ebola outbreak, which began more than a year ago, has finally begun to subside. While the reduction in the number of Ebola patients has given cause for the relaxation of quarantine measures and the reopening of schools, the Ebola outbreak has yet to reach zero new cases in the most affected West African countries.
In the process of assessing the potency of possible countermeasures against the virus, experimental drugs including ZMapp and TKM-Ebola have been utilized to treat some Ebola-infected medical staff who were repatriated to Europe and the United States. The respective contribution of the drugs to patient survival, however, could not be determined due to the absence of experimental conditions.
A different approach has led researchers to replicate human infection in nonhuman primate models to more conclusively assess the efficacy of post-exposure treatments. Recently, researchers from the University of Texas Medical Branch at Galveston and Tekmira Pharmaceuticals Corporation produced the first successful demonstration, to the investigators' knowledge, of the efficacy of a treatment designed to counter the Makona strain of the Ebola virus.
As described in the study printed in the April 22 edition of the journal Nature, the investigators, utilizing a non-human primate model, succeeded in showing the potency of the new treatment, which involves the use of short interfering RNAs (siRNAs). These double-stranded RNA molecules, which were devised to target and interfere with the replication of the Ebola virus, achieved 100% protection for the treated rhesus macaque monkeys.
Three days after being infected by a virus isolated from a lethal case in Guinea, the monkeys were administered the experimental drug TKM-Ebola-Makona. The treated animals not only fully recovered, but also displayed milder clinical features than the untreated animals in the control group during the progression of the disease.
In the treated animals, viral RNA, at a much lower magnitude, was detected in the lymph node and spleen, whereas widespread viral RNA at higher levels were found in the untreated control animals. Moreover, the drug was discovered to provide additional protective benefits against the virus-induced liver and renal dysfunction. Lacking the protection of the drug, the untreated monkeys succumbed to the disease on days eight and nine, a time-to-death which closely mirrored that of human patients following the onset of symptoms.
Besides increasing patient survival and moderating clinical symptoms of the Ebola infection, the siRNA-based treatment approach can potentially confer the additional advantage of being rapidly modified to different viral strains. Though the siRNAs rely on sequence recognition, they can be quickly retooled for distinct viral strains, thus obviating concerns about the limited potency of the treatment.
Currently, a clinical trial involving the TKM-Ebola-Makona drug is underway for Ebola-infected patients in Sierra Leone. Though the decreased number of new Ebola cases marks the end of the suffering of formerly disease-ravaged communities, clinical trials with experimental drugs such as the TKM-Ebola-Makona may be hampered by the lack of patients that can be enrolled.
