DUBLIN, Ireland - BioResearch Ireland (BRI), the state agency for commercializing biotechnology research in Irish universities, has signed an option agreement with Gem Pharmaceuticals for the use of a monoamine oxidase (MAO) inhibitor that preferentially protects healthy cells exposed to irradiation or chemotherapeutic agents.

Gem, based in Pelham, Ala., has a 12-month option to acquire exclusive worldwide licensing rights to the product, code-named GPX-325.

MAO inhibitors block the action of the enzyme MAO, which catalyzes the oxidative deamination of the neurotransmitter dopamine and the hormones epinephrine and norepinephrine.

Low levels of the enzyme are associated with both Parkinson's and depression. Two MAO inhibitor subtypes have been identified, each of which has application in treating one of the two diseases.

Researchers at BRI's National Pharmaceutical Biotechnology Centre (NPBC), based at Trinity College, in Dublin, were investigating the mechanism of one such molecule when they observed that it protected healthy cells and tissue explants from the cytotoxic effects of irradiation and three classes of chemotherapeutic agent.

A Different Response

Transformed cell lines and explants of cancerous tissue did not exhibit the same response to GPX-325, said Margaret Woods, commercial manager of NPBC. The molecule has, therefore, potential application in combination therapies, as it would allow higher doses of radiation or chemotherapy to be administered to cancer patients without damaging healthy tissues.

BRI has filed a Patent Corporation Treaty application to cover the use of both classes of MAO inhibitor as cytoprotective agents. GPX-325 is already in therapeutic use, Woods said, but she declined to specify for which application.

The NPBC team, led by Keith Tipton at Trinity College and Carmel Mothersill at Dublin Institute of Technology, has not yet worked out how GPX-325 mediates its cytoprotective effect. “We don't know what the mechanism is at all,“ Woods said. The NPBC will carry out animal studies in order to work out the details.

Gem Pharmaceuticals, meanwhile, is evaluating its product potential. The fact that GPX-325 is already in therapeutic use means that it will not have to be subjected to a full battery of toxicity tests. Moreover, the molecule was effective at concentrations lower than its current therapeutic dose, Woods said. *