Ebola future or investigational therapies
|
Ebola Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Postmortem Care |
|
Case Studies |
|
Ebola future or investigational therapies On the Web |
|
American Roentgen Ray Society Images of Ebola future or investigational therapies |
|
Risk calculators and risk factors for Ebola future or investigational therapies |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Serge Korjian M.D.
Overview
There are no current antiviral therapies or vaccines for Ebola. Promising results from pre-clinical studies on agents such as ZMapp, AV6001, and TKM-Ebola have led to the development of phase I trials to evaluate the safety of these agents for human use. In August 2014, all Ebola-targeting therapies were granted fast-track designation by the FDA given the expanding outbreak.
Investigational Therapies
Treatment of Ebola virus disease
ZMapp
ZMapp is an experimental drug composed of 3 humanized monoclonal antibodies currently being investigated for the treatment of Ebola virus disease. The component monoclonal antibodies are recombinantly manufactured in a variety of tobacco (Nicotiana benthamiana). It has not yet been tested in humans for safety or effectiveness. Zmapp was studied in a preclinical study involving rhesus macaques exposed to the virus. The drug was successful in rescuing 100% (21/21) of the macaques when the treatment was initiated within 5 day of the Ebola exposure. High grade fever, and significant viraemia was present in many animals before intervention. Full recovery was also observed in animals with advanced disease with elevated liver enzymes, mucosal haemorrhages and generalized petechia. ZMapp was also found to be cross-reactive with the Guinean variant of Ebola. [1]
AVI-6002
AVI-6002 is an investigational drug consisting of positively charged phosphorodiamidate morpholino oligomers (PMOplus). AVI-6002 is a form of antisense therapy whereby a particular gene can be silenced by synthesizing a strand of nucleic acid (DNA, RNA or a chemical analogue) that will bind the messenger RNA (mRNA) produced by that gene. Pre-clinical studies demonstrated that AVI-6002 administered intravenously within 30-60 min of exposure to the virus protects approximately 60% of rhesus monkeys against the Zaire Ebola virus (ZEBOV).[2] A phase I trial that involved 30 healthy volunteers enrolled in six-dose escalation cohorts demonstrated good safety and tolerability of AVI-6002.[3]
TKM-Ebola
TKM-Ebola is a LNP-siRNA (lipid nanoparticle-small interfering RNA). Small interfering RNAs are a class of double-stranded RNA molecules that interfere with gene expression by causing breakdown of mRNA. TKM-Ebola is a combination of siRNAs targeting three of the seven proteins in Ebola virus: Zaire Ebola L polymerase, Zaire Ebola membrane-associated protein (VP24), and Zaire Ebola polymerase complex protein (VP35). A proof of concept study that included monkeys and macquees demonstrated approximately full protection from the virus when the drug was given 30 minutes post-exposure and repeat dosing was administered daily over the next 6 days.[4] In January 2014, a phase I clinical trial evaluating TKM-Ebola in healthy volunteers was announced. Although the study was initially put on hold due to significant flu-like symptoms, the FDA modified this to a partial clinical hold. This action enables the potential use of TKM-Ebola in individuals infected with Ebola virus.[5]
Prevention of Ebola virus diease
VSV-Ebola Vaccine
Given initial data demonstrating the utility of rhabdoviruses as expression vectors with potentials for live viral vaccines, a recombinant VSV (vesicular stomatitis virus) has been investigated as a possible vaccine for Ebola virus disease. VSV is known to grow to very high titers, replicate in almost all mammalian cells, and elicit strong humoral and cellular responses. The recombinant form of the virus would be administered as a live attenuated vaccine that contains Ebola virus viral proteins that illicit antibody formation. In October 2014, the phase I clinical trial to evluate the safety and dosing range of VSV-Ebola was initiated.
References
- ↑ Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB; et al. (2014). "Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp". Nature. 514 (7520): 47–53. doi:10.1038/nature13777. PMID 25171469.
- ↑ Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS, Van Tongeren SA; et al. (2010). "Advanced antisense therapies for postexposure protection against lethal filovirus infections". Nat Med. 16 (9): 991–4. doi:10.1038/nm.2202. PMID 20729866.
- ↑ Heald AE, Iversen PL, Saoud JB, Sazani P, Charleston JS, Axtelle T; et al. (2014). "Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single Ascending Dose Studies". Antimicrob Agents Chemother. doi:10.1128/AAC.03442-14. PMID 25155593.
- ↑ Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V; et al. (2010). "Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study". Lancet. 375 (9729): 1896–905. doi:10.1016/S0140-6736(10)60357-1. PMID 20511019.
- ↑ [| About Investigational TKM-Ebola Therapeutic. Tekmira Pharmaceuticals Corporation.]