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article imageReducing organ rejections using 'lethal' bacterial enzyme

By Tim Sandle     Aug 15, 2017 in Science
Researchers have developed a novel type of drug therapy using an enzyme extracted from bacteria that are normally considered harmful. The aim is to use the enzyme to reduce organ rejection rates following kidney transplants.
At present the drug is at an experimental stage and it is under investigation with a team from the research center Cedars-Sinai. The developed drug is coded IdeS®. Studies to date suggest that treating patients with the drug prior to transplantation significantly reduces, and often eliminates, the donor-specific antibodies that can cause rejection of a new organ (or, in some cases, trigger organ failure). Often the presence of the antibodies (human leukocyte antigens) represents an immunologic barrier to successful organ transplantation. These antibodies cause the body to interpret a newly donated organ as a threat and they move to attack it.
The basis of the IdeS® drug is an enzyme taken from the pathogenic organism Streptococcus pyogenes. This bacterium can be spread via multiple means, including respiratory droplets and hand contact with nasal discharge and skin contact with impetigo lesions. The organism is often present in the mouth and can lead to sore throats; however, diseases of the blood are more serious. Untreated an infection can lead to sepsis or even death.
The enzyme was produced by the company Hansa Medical, located in Sweden. One of the advanced laboratory techniques used to screen enzymes is continuous-flow droplet-based digital Enzyme-Linked Oligonucleotide Hybridization Assay. Digital technologies can also help to detect bacteria; new technology termed ‘Integrated Comprehensive Droplet Digital Detection’ (IC 3D), for example, can selectively detect bacteria directly from milliliters of diluted blood at single-cell sensitivity.
The drug was developed by a team led by Dr. Stanley C. Jordan. In communication to Digital Journal, the researcher explains that the enzyme extracted from the bacterium is the only one identified to date that can completely remove organ-rejecting antibodies and allow for a successful kidney transplantation to take place. The beneficial effects of diffusing the drug into a patient are seen within one hour, at which point the antibody levels fall significantly.
Dr. Jordan states: “We found that IdeS® could immediately cut patient antibodies in half, making them powerless to attack and injure a newly transplanted kidney. We can put a new kidney in a patient without it being rejected.”
The study to date has been with 25 patients, located in Sweden and the U.S. Through the use of the new drug, 24 of the 25 patients have undergone a successful kidney transplant. A larger study is required, however, to verify the consistency of the therapy against a wider patient population.
The research has been published in the journal New England Journal of Medicine. The research paper is titled “IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.”
More about Bacteria, Enzyme, Toxin, Organ, Kidneys
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