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Thread: Many promising anti-Ebola drugs and vaccines are in accelerated production and trial

  1. #1 Many promising anti-Ebola drugs and vaccines are in accelerated production and trial 
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    There are two drugs that have cured monkeys after symtoms show with with ebola. ZMapp (monoclonal antibodies) cured 18 of 18 monkeys several daus out, and TKM Marburg (siRNA) cured 12 of 12 monkeys. (Marburg is almost identical to Ebola.) Furthermore, the NIH has started clinical trials for a new vaccine, which could be available by December. The Canadian health agency plans to start clinical trials in the next few weeks iof another vaccine. See
    ZMapp: Best Anti-Ebola Drug Yet, and http://www.nytimes.com/2014/09/06/wo...says.html?_r=0


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    Making antisense Jon Moulton's Avatar
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  4. #3  
    Making antisense Jon Moulton's Avatar
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    Those are not the only options, nor the farthest into clinical development. Antisense drugs have completed phase I trials. Following are citations of Ebola or Marburg filovirus drug development using Morpholino antisense oligos.

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    Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble CS, Kroeker AD, Iversen PL, Bavari S, Muhlberger E. VP35 Knockdown Inhibits Ebola Virus Amplification and Protects against Lethal Infection in Mice. Antimicrob Agents Chemother. 2006 Mar;50(3):984-93.

    VP35 Knockdown Inhibits Ebola Virus Amplification and Protects against Lethal Infection in Mice

    mice and cell culture

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    Warfield KL, Swenson DL, Olinger GG, Nichols DK, Pratt WD, Blouch R, Stein DA, Aman MJ, Iversen PL, Bavari S. Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers. PLoS Pathog. 2006 Jan;2(1):e1. Epub 2006 Jan 13.

    PLOS Pathogens: Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers

    Rhesus macaque, mouse, guinea pig, Vero cells

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    Vander-Linden CL. Gene-Specific Ebola Therapies Protect Nonhuman Primates from Lethal Diseases. Chem-Bio Defense Quarterly. 2006 3(2):8-9.

    Also this press release from USAMRIID:

    http://www.usamriid.army.mil/press_r...ss_release.pdf

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    Silvestri LS, Ruthel G, Kallstrom G, Warfield KL, Swenson DL, Nelle T, Iversen PL, Bavari S, Aman MJ. Involvement of Vacuolar Protein Sorting Pathway in Ebola Virus Release Independent of TSG101 Interaction. J Infect Dis. 2007 Nov 15;196 Suppl 2:S264-70.

    Involvement of Vacuolar Protein Sorting Pathway in Ebola Virus Release Independent of TSG101 Interaction

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    Swenson DL, Warfield KL, Warren TK, Lovejoy C, Hassinger JN, Ruthel G, Blouch RE, Moulton HM, Weller DD, Iversen PL, Bavari S. Chemical modifications of antisense morpholino oligomers enhance their efficacy against ebolavirus infection. Antimicrob Agents Chemother. 2009 Feb 17. [Epub ahead of print].

    Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus Infection

    mice, cell cultures

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    Iversen PL, Warren TK, Wells JB, Garza NL, Mourich DV, Welch LS, Panchal RG, Bavari S. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections. Viruses. 2012;4(11):2806-2830. doi:10.3390/v4112806.

    Viruses | Free Full-Text | Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

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    Heald AE, Iversen PL, Saoud JB, Sazani P, Charleston JS, Axtelle T, Wong M, Smith WB, Vutikullird A, Kaye E. 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. 2014 Aug 25. pii: AAC.03442-14. [Epub ahead of print]

    Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single Ascending Dose Studies

    human iv infusion

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    Patrick Reid S, Shurtleff AC, Costantino JA, Tritsch SR, Retterer C, Spurgers KB, Bavari S. HSPA5 is an essential host factor for Ebola virus infection. Antiviral Res. 2014 Sep;109:171-4. doi: 10.1016/j.antiviral.2014.07.004. Epub 2014 Jul 11.

    HSPA5 is an essential host factor for Ebola virus infection

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    Clinical trials

    Safety Study of Single Administration Post-Exposure Prophylaxis Treatment for Ebola Virus - Full Text View - ClinicalTrials.gov
    Safety Study of Single Administration Post-exposure Prophylaxis Treatment for Marburg Virus - Full Text View - ClinicalTrials.gov
    A Study to Assess the Safety, Tolerability and Pharmacokinetics of AVI-7288 in Healthy Adult Volunteers - Full Text View - ClinicalTrials.gov
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    Your post makes a completely different point. TKM Marburg and ZMapp are the only two drugs so far, as noted, that have been documented in preclinical trial to repeatedly cure Ebola or Marburg after clear symptoms have arisen. Antisense drugs have not been proven to do this.
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    Making antisense Jon Moulton's Avatar
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    You are right that "there are two drugs that have cured monkeys after symtoms show with with ebola". However, "TKM Marburg and ZMapp are the only two drugs so far, as noted, that have been documented in preclinical trial to repeatedly cure Ebola or Marburg after clear symptoms have arisen" is not true. Post-exposure treatment was reported for rodents with the antisense compounds. On the basis of this and successful prophylaxis in nonhuman primates, the drugs advanced to phase I.

    "A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs) VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also protected 75% of rhesus macaques from lethal EBOV infection."
    Warfield KL, Swenson DL, Olinger GG, Nichols DK, Pratt WD, Blouch R, Stein DA, Aman MJ, Iversen PL, Bavari S. Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers. PLoS Pathog. 2006 Jan;2(1):e1. Epub 2006 Jan 13.
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  7. #6  
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    Hi, again, no, no antisense drugs have been proven to repeatedly cure Marburg or Ebola after symptoms have arisen. Yes, some drugs have been shown to be effective post-exposure. But the key for humans in Africa is whether drugs are going to work after clear symptoms have arisen, because one generally can't know to check oneself for Ebola until one has symptoms. The journal article you cite does not indicate that antisense therapy repeatedly cures after clear symptoms have arisen.
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    Making antisense Jon Moulton's Avatar
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    I agree. The tests reported post-exposure, but not post-symptom, treatment; I was mistaken in my last post. As far as I know that was not tested prior to commencing the human trials.
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    Forum Freshman crushmymugshot112's Avatar
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    • The West African Ebola outbreak is spiraling out of control, especially in Liberia where the number of reported cases is doubling every 10-17 days.
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