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How European research is making kidney transplants safer

Date: 17.6.2013

For those unfortunate to suffer from kidney failure, an organ transplant may seem like the best long-term treatment. But kidney transplants are loaded with risk, the most salient being the rejection of the donor organ by the host’s body. Now, however an Irish-led research project has developed a new drug that could succeed in preventing organ rejection, offering hope to thousands of patients seeking donor kidneys.

The project is the result of the collaboration by nine European research and clinical groups under the banner of MABSOT, or Monoclonal Antibody Solid Organ Transplantation. It aims to develop a drug, OPN-305, to treat delayed graft function (DGF), which is defined as the need for dialysis in the first week after surgery. DGF occurs in 40% to 60% of patients receiving a transplant from higher risk donors but OPN-305, an antibody developed to reduce inflammation, could lessen this complication.

The MABSOT consortium is led by Opsona Therapeutics, an Irish drug development SME spun-out from Trinity College Dublin, which last year won an Outstanding Achievement Award at Ireland’s Champions of EU Research event. The consortium aims to ensure transplants from non-living donors – considered more high risk – are used more frequently. “Because of the lack of available organs, surgeons have to use more kidneys that are less than ideal, and there is a risk they don’t work or work poorly,” says Opsona co-founder Luke O'Neill. “Our drug essentially should allow such kidneys to work better from the outset and improves the chances of long term success.”

O'Neill is also Chair of Biochemistry at Trinity College Dublin, Chair of the Immunity and Infection panel of the European Research Council (ERC), an ERC Advanced Grant awardee and also a recent recipient of a Gold Medal Award from the Royal Irish Academy. He explains that OPN-305 works by stopping the inflammatory process from rejecting the kidney, acting to prevent an acute inflammatory reaction, which might stop the kidney from working.

OPN-305 is an antibody to TLR-2, which is one of the key structures of the innate immune system and part of the first line of defence against microbial organisms. When stimulated, TLR-2 induces and propagates inflammation. It is activated through so called external danger signals like microbial cell wall components, as well as through so called internal danger signals resulting from tissue injury. “TLR-2 is present in the kidney, senses the trauma of the transplant and drives the acute inflammation,” says O’Neill. “However, OPN-305 blocks the TLR-2 from working and causing mischief, and so blocks that acute inflammatory process.”

Mary Reilly, Opsona’s Vice President for Pharmaceutical Development and Operations and Coordinator of the Mabsot project, says OPN-305, which has already been granted patents, can be used for other organs too. “Anywhere that you see ischaemia – the starving of oxygen from organs – then the antibody has the potential to protect. You can extend this potential to heart, liver and lung transplants, as well as treatments for heart attacks, stroke or cancer,” she says.

There have so far been several successful transplants performed using OPN-305 as part of the study. Reilly says approval based on successful clinical trials could be by 2019. She says the promise of speedy and effective transplants would be a huge relief to patients, improving their chances of a decent quality of life free from clinics and dialysis machines.

It would also be a remarkable research success story, Reilly notes. “There is a lot of interest in the novel aspects of this product, and it can be considered first and best in class if the clinical study is successful. We really are at the cutting edge of this: there is nothing out there approved for this indication,” she says.

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