New therapy may eliminate transplant patients’ need for lifelong drug intake

March 02, 2013

By AKIYOSHI ABE/ Staff Writer

A team of Japanese researchers has developed a technique that prevents a patient’s body from rejecting transplanted organs, eliminating the need for a lifelong regimen of immunosuppressant drugs.

The technique, developed by medical researchers at Hokkaido University and Juntendo University in Tokyo, involves manipulating the recipient’s and the donor’s white blood corpuscles, which play a key role in immune rejection.

The team conducted trials on 10 subjects who received liver transplants from living donors. Four of them have not had to take immunosuppressant drugs for up to six months, while the six others have reduced their doses.

The method is expected to significantly ease the difficulties facing transplant recipients once it is established as a new form of therapy.

Transplant recipients typically have to continue taking drugs for the rest of their lives to prevent immune rejection. The resultant reduced immunity levels not only enhance the risks of infection and cancer, they can also lead to kidney failure and other serious side effects.

Immune rejection occurs when the recipient’s T cells–a type of white blood corpuscles–attack the transplanted organ, which they recognize as a foreign body.

Hokkaido University organ transplantation professor Satoru Todo, Juntendo University immunology professor Ko Okumura and coworkers extracted white blood corpuscles from the blood of both the recipient and the donor prior to a transplant and co-cultured them. They added a special agent so that the recipient’s white blood corpuscles mistook donor-derived components for the recipient’s own.

The cultured white blood corpuscles were returned to the recipient two weeks after the transplant, and the recipient’s immunosuppressant drug intake was reduced in stages.

The trials, which started in November 2010, were conducted on 10 individuals in their 30s through their 60s, who had developed cirrhosis of the liver due to hepatitis or cholangitis. Four of them stopped taking drugs 18-21 months following their transplants, and as of the end of February had been free of medication for periods ranging between six weeks and six months. The remaining six have reduced their drug intake, with five of them expected to eventually stop taking the drugs altogether, the researchers said.

About 500 liver transplants take place every year in Japan. The five-year survival rate stands at about 80 percent. A method to effectively block immune rejection without the use of medication is expected to help enhance both the survival rate and the quality of life of the recipients.

The researchers said they want to establish the new technique as a therapy only after ensuring its effectiveness and safety over an extended period of time, because some forms of immune rejection can arise many years following transplants.

A separate joint study by Juntendo University and Tokyo Women’s Medical University, which started five years ago, has applied the same kind of technique to kidney transplants from living donors and has managed to reduce medication doses considerably.

The new technique could also be used to help treat rheumatism and other autoimmune diseases that arise when white blood corpuscles attack a patient’s own body, mistakenly identifying it as foreign.

“Theoretically, (autoimmune diseases) can be cured if the self-attacking white blood corpuscles can be taught that the body is not foreign,” Okumura said.

The research results will be presented to an annual meeting of the American Transplant Congress in May.

By AKIYOSHI ABE/ Staff Writer

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