PYC pyc therapeutics limited

PPMOs fight antibiotic resistance

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    Phylogica recently announced the outcome of studies which confirmed that a cell penetrating Phylomer improved the intracellular delivery of an oligonucleotide. In that announcement Richard Hopkins said, “We’ve now shown we can deliver a whole new class of drug that has the potential to open up commercial opportunities in the oligonucleotide field, which has seen a significant resurgence over recent years.”

    Surprisingly, one of those potential opportunities could lie in addressing the growing problem of antibiotic resistance.

    Researchers at UT Southwestern Medical Center have been studying the use of PPMOs (peptide-conjugated phosphorodiamidate morpholino oligomers) to target the efflux pump found in bacterial cell walls. The efflux pump system contributes to antibiotic resistance not only by expelling a broad range of antibiotics from bacterial cells but also by driving the acquisition of additional resistance mechanisms by lowering intracellular antibiotic concentration and promoting mutation accumulation. The PPMO doesn't work by killing the bacteria; rather, it keeps it from expelling the antibiotic, meaning the antibiotic drug can remain intracellular for longer periods in order to do its job.

    In a recent study, using the CPP (RXR)4XB, the UT Southwestern researchers demonstrated that a PPMO designed to prevent creation of the AcrA protein significantly increased the efficacy of antibiotics against E. coli in cell models from two- to 40-fold. It was also found that some antibiotics that are never used against E. coli because they were thought to be ineffective, killed the bacteria, when used in conjunction with the AcrA-PPMO. Importantly, no cytotoxicity was observed.

    The researchers believe that use of PPMOs offers the potential to improve efficacy of existing antibiotics, lower the antibiotic doses required, reduce side effects, allow use of some antibiotics for treating infections against which they are normally not effective and allow use of antibiotic pairs even if the two drugs partly work against each other’s inhibitory effects.

    As a further positive, the researchers observed that acquired bacterial resistance to PPMOs could be overcome by attaching a different peptide to the same oligomer, which had the effect of rescuing PPMO activity.

    PPMOs would seem to be yet another approach to tackling antibiotic resistance and yet another commercial opportunity for Phylogica’s FPP delivery platform.

    http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002552

    https://www.sciencedaily.com/releases/2016/09/160917132345.htm

    http://www.future-science.com/doi/abs/10.4155/tde.13.145
 
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