Antioxidant drugs extend lifespan - in nematodes

In a collaborative effort, scientists have for the first time successfully increased normal lifespan in the nematode worm C. elegans through the use of drugs that augment the organism's natural antioxidant systems. As reported in the September 1, 2000 issue of Science, it appears confirmed that oxidative stress is a major determinant of lifespan—at least in the nematode—and that it can be counteracted by pharmacological intervention.

The findings are the result of a research collaboration, initiated by Simon Melov of the Buck Institute (Novato, CA). The project included Gordon Lithgow and colleagues of the University of Manchester (UK), Doug Wallace of Emory University (Atlanta) and Susan Doctrow and Bernard Malfroy of Eukarion Inc. (Bedford, MA).

The experiments involved groups of adult nematodes that were either untreated or treated with synthetic catalytic scavengers, or SCSs. These drugs are synthetic versions of superoxide dismutase and catalase, naturally ocurring enzymes involved in the control of oxidative stress. The team of researchers found that treatment of adult wild-type nematodes with synthetic superoxide dismutase/catalase mimetics had mean lifespans that were on average, approximately 50% longer than the untreated nematodes. Furthermore, in a mutant nematode strain with a shortened lifespan linked to oxidative stress, an early death was prevented and lifespan normalized through treatment with the drugs. Results suggest that endogenous oxidative stress is a major determinant of the rate of aging.

Nematodes have been used for years to study biological processes relevant to other species, including humans.

"These results are the first real indication we have had that aging is a condition that can be treated through appropriate drug therapy," said Melov, a founding faculty member of the Buck Institute, who initiated the pilot studies. "Further studies on higher organisms will allow us to answer whether or not we have to reconsider aging as an inevitability."

"We have been working on our proprietary synthetic SCS compounds for several years," said Bernard Malfroy, CEO of Eukarion. "To date, the compounds have been successfully used in models of neurodegenerative, cardiovascular, autoimmune and inflammatory diseases. This work on nematode lifespan further strengthens our belief that SCSs have tremendous potential as therapeutics. Our priority now is to move these compounds toward clinical trials."

The Buck Institute and Eukarion will continue to collaborate on the role of SCSs in aging, now with an eye towards advancing products toward clinical development.

The Buck Institute is dedicated towards extending healthy, productive lifespan through basic research. Since opening in July 1999, the institute has focused on why we develop diseases as we age and developing therapeutics to prevent these debilitating conditions. The Buck Institute is a non-profit, independent organization and seeks funding from government, foundation, corporate, and other sources to accomplish its mission. For further information visit the web site at www.buckinstitute.org.

Eukarion Inc., a privately held biopharmaceutical company, develops small molecule drugs for treationg of degenerative and age-related disorders. The company's principal focus is on its patented synthetic catalytic scavenger (SCS) technology for the treatment of conditions related to oxidative stress. Eukarion holds five U.S. patents for its SCS technology and has been awarded over $2.8 million in grants from the National Institutes of Health to further its research and development goals.

For more information: Bernard Malfroy, Eukarion Inc., 6F Alfred Circle, Bedford, MA 01730. Tel: 781-275-0424. Fax: 781-275-0752.

Edited by Angelo DePalma
Managing Editor, Drug Discovery Online