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Protective strategy shields primate ovaries from radiation-therapy-induced damage
Date:2/22/2011

ly and colleagues at Memorial Sloan-Kettering Cancer Institute reported in 2002 that S1P-pretreated female mice that were mated two months after receiving radiotherapy successfully delivered litters of healthy offspring.

Testing this approach in primates presented several challenges, so before attempting a trial in monkeys, the researchers wanted to be sure that S1P would also protect human oocytes. Ovarian tissue from human patients was grafted into immunodeficient mice, and some of the animals were treated with S1P for an hour before the tissue was exposed to radiation. The experiment showed that the resting pool of follicles from which oocytes develop into mature eggs was protected in the S1P-treated animals but was largely depleted in the human grafts not protected with S1P.

Another potential obstacle to bringing this approach from mice to primates is the fact that rodent ovaries are enclosed in a membrane sac, confining any drug injected into the sac to the ovary. Primate ovaries are free of any such enclosure, presenting the risk that any protective agent applied to the ovary might escape and protect tumor cells as well. Fortunately, investigators at the Oregon National Primate Research Center based at OHSU had already developed an implantable miniature pump that could deliver a drug to the ovaries alone.

In the current study, the OHSU team, led by Mary Zelinski, PhD, conducted a series of experiments, the first of which confirmed that delivering S1P directly to the ovaries of rhesus monkeys provided the same sort of protection from radiation effects seen in the earlier mouse studies. Since S1P is a rather unstable molecule that is broken down quickly, the researchers then tried using FTY720, a long-acting S1P-like agent with similar effects that also is approved for the treatment of multiple sclerosis. Treatment with FTY720, also called fingolimod, was even more successful than S1P in protecting monkey ovarian follicles fr
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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