Unexpected discovery could lead to development of immunity defense against antibiotic-resistant germs
In a groundbreaking discovery, researchers at Johns Hopkins Medicine have found a new potential solution to the threat of antibiotic-resistant bacterial infections. This immune-based treatment, which could mark the start of a second golden age of immunotherapy, was published in the journal Science Translational Medicine.
The research, led by Lloyd Miller, M.D., Ph.D., initially aimed to study the mechanisms behind MRSA skin infections in mice with and without the ability to manufacture interleukin-1 beta (IL-1β). The team tested a compound called Q-VD-OPH, a pancaspase inhibitor, on Streptococcus pyogenes, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA), finding success similar to that with MRSA.
The use of pancaspase inhibition for targeting the body's immune system against bacteria is referred to as "host-directed immunotherapy". The treatment works whether IL-1β is present or not, and without administering any antibiotics.
The pancaspase inhibitor reduces apoptosis of neutrophils and monocytes, leaving them in plentiful numbers and better able to remove MRSA bacteria. Enhanced necroptosis of macrophages, which are mature monocytes, was also observed with the treatment.
A single oral dose of Q-VD-OPH decreased the size of MRSA skin lesions and rapidly cleared the bacteria compared with vehicle-treated and untreated mice. The study's data was included in a U.S. patent application (PCT/US2021/024889) through Johns Hopkins Technology Ventures for "caspase inhibition as a host-directed immunotherapy against bacterial infections".
The research was supported by grants from the National Institute of Allergy and Infectious Diseases, and the National Institute of Arthritis, Musculoskeletal and Skin Diseases. The authors of the 2021 paper in Science Translational Medicine are not identified in the provided search results, but the research team includes Miller and several other researchers from Johns Hopkins Medicine.
It is important to note that Miller is a full-time employee of Janssen Research and Development, and has received grant support and held stock from various pharmaceutical companies. However, none of the other authors have financial disclosures or conflicts of interest related to this study.
Miller expresses hope that the success of this study could mark the start of a second golden age of immunotherapy. The discovery of penicillin by Alexander Fleming in 1928 led to the era of antibiotics, but the increasing resistance of bacteria to antibiotics has made the need for new treatments more urgent. This potentially game-changing treatment offers a promising alternative.
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