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Two Young Companies Use Microarrays in Quest for Biomolecular Fountain of Youth

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While a number of researchers are using microarrays to pan for diagnostic gold, two companies are hoping to go one step beyond that — to the molecular fountain of youth. Gene expression profiles, they believe, could reveal the secrets of aging, and how to delay it.

Both companies are at a young stage in their own lives and have a lot in common — until recently even the sound of their names: LifeGen Technologies and LifeSpan Genetics.

LifeSpan, which changed its name last month to BioMarker Pharmaceuticals to avoid a legal battle with another company, is majority-owned by the Life Extension Foundation, a nonprofit organization with 77,000 members worldwide that funds scientific research aimed at preventing and treating disease, aging, and death. The foundation is financed through membership dues and a for-profit arm that sells dietary supplements. Saul Kent, a co-founder of the Life Extension Foundation, co-founded LifeSpan/BioMarker along with Stephen Spindler, a professor of biochemistry at the University of California, Riverside, and Victor Vurpillat, who had experience with startup companies, in November 1999. Spindler had been working for several years on caloric restriction — described by some as “under-nutrition without malnutrition” — and its effects: extending lifespan and delaying age-related diseases like heart disease and diabetes in mammals.

LifeSpan’s idea to use microarrays to search for the secrets of aging was backed by a 1999 paper in Science, authored by a group of researchers at the University of Wisconsin, Madison, who used high-density oligonucleotide microarrays to study gene expression profiles associated with aging and caloric restriction in mice. The researchers found that the gene expression patterns seemed to reflect the biological age of the tissue, and that caloric restriction changes it within a short time. Realizing the promise of the technology, LifeSpan invited two of the authors, Richard Weindruch, a professor of medicine, and Tomas Prolla, an assistant professor of genetics, to join the company. “With DNA microarrays, one potentially can do large-scale studies where many compounds or many genetic interventions are investigated, … over a period of a life span as opposed to the entire life span,” Prolla commented.

But Weindruch and Prolla’s collaboration with LifeSpan was to be short-lived. The relationship deteriorated over “a difference in opinion on the direction that the company should go,” said Spindler, especially on the assay technology. As a result, Weindruch and Prolla founded their own company, LifeGen Technologies, in November 2000. Both companies have a co-exclusive license to a patent application from the University of Wisconsin covering the use of DNA microarrays to measure biological age, but both have applied for other patents separately.

LifeSpan, now BioMarker, has followed the drug discovery pathway, testing compounds for their ability to mimic gene expression profiles associated with caloric restriction or life-extending mutations, and hoping that they will have the same beneficial effects on aging or age-related diseases. “We can screen pharmaceuticals in a matter of weeks to see if they can reproduce the profiles that we know are associated with those beneficial effects,” said Spindler. He hopes to perform these assays in partnership with other companies either on compounds in the drug discovery pipeline or on already existing drugs.

To do the initial screening, Spindler has been using a variety of Affymetrix arrays, as well as cDNA arrays containing about 3,000 genes of interest for aging and disease. So far the gene expression studies have been limited to mice and — in collaboration with the NIH — monkeys, but Spindler said studies in humans are soon to come. Microarrays, he said, will be important initially but other technologies will be needed further downstream.

BioMarker currently has a staff of five, “employed by the company either directly or indirectly,” who all work in Spindler’s laboratory, he said. However it is hoping to move into its own facilities at Riverside next month, according to Vurpillat.

LifeGen Technologies, on the other hand, does not have a single employee, but has already rented and equipped 2,000 square feet of lab space at the research park in Madison. It is currently looking for investors and has had “pretty advanced discussions with some people already,” Prolla said. Also, LifeGen has an ongoing research partnership with Purina to test and identify nutritional factors that can retard the aging process in animals. Prolla thinks the growing market for functional foods for humans is very promising for his company: “One of the major problems in the field is the lack of scientific validation. We think that by using DNA microarrays … we can provide substantiation to health claims.”

LifeGen also plans to generate tools to measure biological age, and to identify targets for age-delaying drugs. So far, it has used a variety of Affymetrix arrays in its studies of mice and rhesus monkeys. In the coming months, the company wants to put together a research team and identify further partners. But Prolla’s long-term vision seems almost Utopian at present: “What we are talking about is not only understanding the aging process, it is in fact understanding human health,” he said, “because if one could keep animals or people in a state which is biologically young, most diseases would be avoided.”

— JK

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