Preventing donor organ rejection

I wrote this article for my print module coursework… I found it really interesting, and I hope you do too!

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Can you begin to imagine the devastation when someone learns that after waiting months, possibly even years, for a donor organ to replace their own ailing one, their body has ruthlessly rejected it? Unimaginable? Unfortunately, for some transplant patients this is a heartbreaking reality.

However, donor organs are, by and large, accepted by transplant patients’ bodies. This is due to the powerful cocktail of immunosuppressant drugs that they take for the rest of their lives. These dampen the body’s immune system, weakening its effects and protecting the donor organ. However, it is not an ideal situation, as long-term pharmacological intervention is not without its dangers. “These drugs affect the immune response throughout the body, increasing the chance of infection and cancer… Clinical transplantation has only had the success that it has because of the pharmaceutical companies. They have done a fantastic job but there is a need for a more sophisticated method [of preventing organ rejection],” explained Dr. Andrew Bushell, Senior Post-Doctoral Fellow at Oxford University’s Transplantation Research Immunology Group.

An international research team, led by Dr Bushell, is working to develop such a method. In April the group published a study in Science Translational Medicine that showed that certain cells in the immune system, regulatory T cells (T-regs), could be taught to recognize a donation as its own, removing the need for prolonged use of immunosuppressant drugs. Although this cellular therapy would not be strong enough to totally eliminate the need for the drugs, it would free transplant patients from a lifetime of taking powerful medication.

This study was published alongside two other papers in the same issue of Science Translational Medicine. The teams behind the three publications are part of a larger group of researchers in Europe who are involved in the ONE Study, whose primary aim is to prevent transplanted organ rejection without the need for immunosuppressant drugs. With this aim in mind, the Oxford researchers are looking to start human clinical trials as early as 2013. “We’ve got the patients, we’ve got the funds, and the clinicians are on side, so it will happen. The question is whether this will be a safe treatment?” explained Dr Bushell.

The results from the first human trial which used T-reg cellular therapy to control a condition similar to organ transplantation rejection were published this earlier year by a team at the University of Minnesota.  “The main risk was severe allergic reaction (anaphylaxis), and that did not occur.  We did not see any other long-term risks either,” explained Dr Claudio Brunstein, who led the study. The group is currently building on their initial research. “We are planning to test a higher dose in more patients, and then perform a randomised trial to confirm the efficacy of the cells,” said Dr Brunstein. This is encouraging for the Oxford University team. “On the back of that [research] we hope to get ethical approval [for our clinical trials],” said Dr Bushell.

Although not the only route that researchers are exploring to eliminate the need for immunosuppressant drugs, the manipulation of the body’s own immune system through harnessing the power of T-regs seems to be one of the most promising. “It’s not right to say that T-regs are superior [than other treatments], because no one knows, but [other options] are currently only possible in a minimal number of patients,” Dr Bushell said.

Although it cannot take away the heartbreak of those who have already had donation rejected, a non-invasive cellular therapy could be a reality soon.  Importantly, this therapy would allow transplant patients to live a healthier life as well as preventing the rejection of donor organs.

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