THERE’S a better way to deal with rejection. People who have received a donor organ need to take a host of toxic drugs to stop their immune system attacking it. Soon they might just have their immune system rebooted – making it accept the new organ.
The technique has been tried for the first time on 20 kidney transplant recipients. Normally they would have to take up to 20 drugs daily, with a risk of developing kidney failure or cancer, as well as side effects such as bloating and diarrhoea.
The group took part in a trial led by Allan Kirk of Emory University in Atlanta, Georgia. He reset their immune system so that it tolerates their new kidney. Seven of them now need only a single injection each month. The other 13 have the injection plus one daily pill (American Journal of Transplantation, doi.org/r5j).
Transplant surgeons have hailed it as a watershed. “I think it will be a big stride forward, getting tolerance for solid organs,” says Roy Calne, who pioneered simultaneous transplants of multiple organs. “Most of all, it’s a big advance in comfort for the patients.”
The treatment developed by Kirk’s team has three main components. The first is a drug called alemtuzumab, given intravenously during the transplant surgery. It wipes out the white blood cells, or lymphocytes, that would otherwise attack the new organ.
Lymphocyte numbers recover over the following 12 to 18 months, but these cells accept the kidney as “self” rather than foreign tissue. “It hits the reset button for the immune system,” says Kirk.
“The new white blood cells accept the donated kidney as ‘self’. It’s like hitting the reset button”
A second drug called belatacept encourages the new white blood cells not to reject the organ. Injections of the drug are frequent at first, but become monthly six months after the transplant.
Finally, the patients receive a daily pill of a mild immune suppressant called sirolimus. It mops up any older lymphocytes that survived the dose of alemtuzumab.
A year after surgery, no one in the group had symptoms of organ rejection or any need to take the standard post-transplant drugs. At this point, Kirk asked 10 of them if they wanted to stop taking sirolimus. All but three did so. Now these seven people have monthly injections of belatacept alone. Three-and-a-half years after the first transplants took place, all 20 people in the study continue to do well on the treatment.
Since this first trial, Kirk has treated another 18 kidney transplant recipients, who are now being weaned off sirolimus. He is also planning a much larger trial, to start next month.
Ultimately, Kirk hopes it will be possible to tweak the treatment so that even belatacept is unnecessary. He tried taking two people off it, but had to restore the drug after hints of rejection. He also hopes to try the treatment in other organ transplants. He is confident the effects will be lasting, as even people on belatacept alone haven’t produced antibodies that would attack their new kidney. What’s more, a potential stumbling block over the cost of the treatment has been overcome (see “Right drug, but will the price be right?“).
Calne says Kirk’s approach is the mildest and most practical attempt so far to “tolerise” the body to transplanted organs. “Many are much harsher, involving body irradiation for example, or multiple injections of drugs. None have been anything like as successful.”
Right drug, but will the price be right?
Kidney transplant recipients might no longer have to take the customary cocktail of anti-rejection drugs, thanks to a new treatment (see main story). But for a while it seemed that a key part of the treatment – a drug called alemtuzumab – would become unaffordable for many people who need transplant surgery.
Last year Genzyme, the company that makes it, received approval in Europe to sell the drug as a treatment for multiple sclerosis (MS). Genzyme then stopped selling it for use in treating a type of leukaemia, with the intention of relaunching it. This would let it be sold at a much higher price, in line with other MS drugs.
But Genzyme this week confirmed that it will make the drug available free of charge “on a named patient basis” – to individuals with a particular need for it – whether for transplant surgery or leukaemia. The company told New Scientist it will do so “for the foreseeable future”.
The pioneering transplant surgeon Roy Calne warns that makers of immune suppressant drugs may yet oppose Genzyme’s move, as their own business may suffer as a result. At Calne’s behest, the whole issue will be discussed at a special session of the annual meeting of the Transplantation Society – an international non-profit body – in July. The goal is to reach long-term deals to ensure access to alemtuzumab.