Publication Date: Wednesday Jan 27, 1999

GERON RESEARCH: Menlo Park's Geron leads the way in anti-aging technology

If 16th century Spanish explorer Ponce de Leon were alive today, he'd probably be on his way to Menlo Park, where Geron Corp.'s groundbreaking work in creating immortal cells is attracting international attention. Geron, a biopharmaceutical company founded in 1992, is the world leader and pioneer in the understanding of fundamental age-related biological mechanisms. The company's unrivaled expertise lies in its research into telomeres, structures at the end of chromosomes that Geron has shown to act as a molecular "clock" of aging in normal human cells, and telomerase, an enzyme that rewinds the "clock," conveying replicative immortality to cells.

Although these biological mechanisms sound obscure, they may hold the best promise of helping prevent or reverse age-related diseases such as Alzheimer's or AIDS. They may usher in a new era of cell therapies for use in transplants and heart disease. And they may lead to drugs that diagnose and even stop the spread of cancer.

"There's certainly been excitement within the scientific community (about Geron's research)," said Alan Goldhammer, executive director for technical affairs for the Biotechnology Industry Organization in Washington, D.C.

"The biotech industry has created a lot of new tools in molecular biology that have made it more realistic for research to move into the private sector, like Geron, so commercial applications can be developed," says Goldhammer. "It's going to lead to more therapies and other advances in health care for diseases and chronic conditions that are related to aging, including cancer."

Geron, led by chief scientist Calvin Harley, is currently researching three complementary areas of product development, all using telomeres and telomerase: aging cells, cancer cells and embryonic stem cells. Each successful step builds upon the other to help the company reach its goals.

"We aren't looking to necessarily increase somebody's life span directly," said Nancy Robinson, Geron's head of investor and media relations and a former molecular biologist. "Our mission is to improve people's health within their life span."

Normal human cells are mortal. Each time they divide, telomeres, located at the end of the chromosomes, get shorter. The cells eventually become "senescent," or old, no longer dividing and no longer carrying out normal metabolic functions. These cells are believed to contribute to age-related diseases because they make different proteins than young, healthy cells.

Telomerase is a rare and complex "immortalizing" enzyme found naturally in reproductive cells, or embryonic stem cells, allowing genetic information to be passed from generation to generation. It is also abnormally activated in cancer cells, allowing them to divide enough times to grow and metastasize in potentially deadly ways.

First, Geron finished cloning human telomerase in test tubes in August 1997. In January 1998, Geron discovered that inserting active telomerase into normal mortal cells resulted in the lengthening of the telomeres and a marked increase in the cells' life spans, making them potentially immortal.

The fear, however, was that doing so would make the newly immortal cells cancerous. But recently published study results by Geron on mice--equipped with bioengineered human skin and retina cells injected with telomerase--showed that the enzyme can be safely used to extend the life span of human cells without making them cancerous. This breakthrough, recently published in the journal Nature Genetics, paves the way for the possible treatment of humans for age-related diseases.

Geron is also trying to turn off telomerase in cancer cells, making them, in turn, mortal and easier to kill. Because telomerase is not active in most normal cells, inhibiting telomerase could prove to be a more effective approach to cancer therapy. Current cancer treatments tend to kill healthy cells along with diseased cells, resulting in serious side effects.

In addition, detecting telomerase and its activity can help diagnose and monitor cancer. "Telomerase is found in every type of cancer we've looked at," said Robinson. "It's a very nice and very specific universal cancer marker."

Geron's stem cell research may be especially useful in creating new therapeutic applications, such as growing heart muscle cells for heart disease patients, or bone marrow cells for bone marrow transplants. It may even become possible to grow tissues or entire organs in the lab.

Human testing is at least several years away, says Robinson. In the meantime, Geron will continue testing drugs and chemicals that start or stop telomerase activity in cells, and then move on to animal testing. 

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