Find may slow aging (8/14/1997)

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Find may slow aging
Cloned protein: Discovery could lead to effective anti-cancer drugs.

Published: Aug. 15, 1997
BY JIM PUZZANGHERA
Mercury News Staff Writer
Researchers have discovered what has been referred to as the holy grail of cell aging -- a find with great potential for combating cancer as well as for staving off the maladies of old age.
More precisely, two separate scientific teams -- one from Geron Corp. of Menlo Park and the University of Colorado, the other led by researchers at the Whitehead Institute for Biomedical Research of Cambridge, Mass. -- announced Thursday that they have been able to clone a protein that controls how long cells live.
The discovery could lead to anti-cancer drugs in the next decade and someday perhaps a pill that would convey the magical properties of the mythical Fountain of Youth.
``This is not just a very interesting scientific discovery. It has very practical applications,'' said Ronald Eastman, president and chief executive officer of Geron, a biotech company that already is working to develop drugs to combat cancer and aging. ``For the first time, we have the opportunity to enhance the lifetime of a normally dividing cell.''
The protein whose genetic code scientists have duplicated affects the tips of DNA, the tiny molecules in our cells that contain the instructions for life. In normal cells, those tips -- called telomeres -- act like a burning fuse, shortening each time the cell divides and ultimately triggering the cell's death.
In cancer cells, however, the protein somehow fires up an enzyme called telomerase that prevents the DNA tips from shortening. That allows the uncontrolled cell growth that creates tumors.
Now that the genetic sequence for the protein has been cloned, researchers said they can use that information to make early diagnoses of cancer and try to find drugs that would short-circuit the protein. That would cause cancer cells to die without damaging normal cells -- a problem with conventional chemotherapy and radiation treatments.
Conversely, adding the protein to normal cells, which do not have it, could make them live longer, postponing age-related diseases such as osteoporosis and atherosclerosis.
``It's an exciting discovery,'' said Sudhir Srivastava, program director of the Early Detection Branch of the National Cancer Institute.
Geron's research appears in today's issue of Science. The research from the Whitehead Institute will appear in the Aug. 22 issue of the journal Cell.
Telomerase is found in 99 percent of cancer tumors, Srivastava said -- an amazing figure for a disease that has so many different forms. He has been working on using the presence of telomerase in cells as an early signal of cancer and said having the exact genetic code of the protein will be very important to his work.
Scientists said the anti-cancer uses of the protein are closer to reality than uses to prevent aging because it's less complicated to block a protein's function than to insert a working version into a cell -- in the same way that there are more ways to get a car's engine to stop than there are to get it started.
``It's not the answer to cancer, but it may be an answer to cancer,'' said Dr. Robert Weinberg of the Whitehead Institute, who led the research team there that decoded the protein.
Both teams benefited from the ongoing Human Genome Project, a multibillion-dollar initiative to decode the entire human genetic code. Researchers on that project post their newly decoded sequences in a public database.
One recently decoded section of the human genome that appeared in the database closely matched decoded versions of the telomerase protein found in simple life forms such as yeast. That helped Geron and Whitehead researchers find the human version.
The twin discoveries of the gene sets up a potential battle over what could turn out to be a very lucrative biotech patent. But Geron officials believe they have a strong claim because the discoveries build on earlier work by a member of their team, Nobel Prize winner Thomas Cech of the University of Colorado in Boulder.
And two years ago, Geron cloned a different component of telomerase, which it has patented.
Geron is already working to develop drugs to combat cancer and aging. Two of the world's leading pharmaceutical companies -- Pharmacia & Upjohn, and Japan's Kyowa Medex -- have signed deals in the past year to pump as much as $88 million in to Geron to develop anti-cancer drugs.
Eastman said the company has been working for more than a year to develop a cancer drug that would inhibit telomerase and hope to have one ready for human tests in the next one to three years. Two companies already have licensed Geron's telomerase-detection technology for diagnostic kits for cancer research use and hopes to sign a deal with a large pharmaceutical company to develop diagnostic kits for routine medical use, he said.
Posted at 10:04 p.m. PDT Thursday, August 14, 1997

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Find may slow aging Cloned protein: Discovery could lead to effective anti-cancer drugs. Published: Aug. 15, 1997 BY JIM PUZZANGHERA Mercury News Staff Writer Researchers have discovered what has been referred to as the holy grail of cell aging -- a find with great potential for combating cancer as well as for staving off the maladies of old age. More precisely, two separate scientific teams -- one from Geron Corp. of Menlo Park and the University of Colorado, the other led by researchers at the Whitehead Institute for Biomedical Research of Cambridge, Mass. -- announced Thursday that they have been able to clone a protein that controls how long cells live. The discovery could lead to anti-cancer drugs in the next decade and someday perhaps a pill that would convey the magical properties of the mythical Fountain of Youth. ``This is not just a very interesting scientific discovery. It has very practical applications,'' said Ronald Eastman, president and chief executive officer of Geron, a biotech company that already is working to develop drugs to combat cancer and aging. ``For the first time, we have the opportunity to enhance the lifetime of a normally dividing cell.'' The protein whose genetic code scientists have duplicated affects the tips of DNA, the tiny molecules in our cells that contain the instructions for life. In normal cells, those tips -- called telomeres -- act like a burning fuse, shortening each time the cell divides and ultimately triggering the cell's death. In cancer cells, however, the protein somehow fires up an enzyme called telomerase that prevents the DNA tips from shortening. That allows the uncontrolled cell growth that creates tumors. Now that the genetic sequence for the protein has been cloned, researchers said they can use that information to make early diagnoses of cancer and try to find drugs that would short-circuit the protein. That would cause cancer cells to die without damaging normal cells -- a problem with conventional chemotherapy and radiation treatments. Conversely, adding the protein to normal cells, which do not have it, could make them live longer, postponing age-related diseases such as osteoporosis and atherosclerosis. ``It's an exciting discovery,'' said Sudhir Srivastava, program director of the Early Detection Branch of the National Cancer Institute. Geron's research appears in today's issue of Science. The research from the Whitehead Institute will appear in the Aug. 22 issue of the journal Cell. Telomerase is found in 99 percent of cancer tumors, Srivastava said -- an amazing figure for a disease that has so many different forms. He has been working on using the presence of telomerase in cells as an early signal of cancer and said having the exact genetic code of the protein will be very important to his work. Scientists said the anti-cancer uses of the protein are closer to reality than uses to prevent aging because it's less complicated to block a protein's function than to insert a working version into a cell -- in the same way that there are more ways to get a car's engine to stop than there are to get it started. ``It's not the answer to cancer, but it may be an answer to cancer,'' said Dr. Robert Weinberg of the Whitehead Institute, who led the research team there that decoded the protein. Both teams benefited from the ongoing Human Genome Project, a multibillion-dollar initiative to decode the entire human genetic code. Researchers on that project post their newly decoded sequences in a public database. One recently decoded section of the human genome that appeared in the database closely matched decoded versions of the telomerase protein found in simple life forms such as yeast. That helped Geron and Whitehead researchers find the human version. The twin discoveries of the gene sets up a potential battle over what could turn out to be a very lucrative biotech patent. But Geron officials believe they have a strong claim because the discoveries build on earlier work by a member of their team, Nobel Prize winner Thomas Cech of the University of Colorado in Boulder. And two years ago, Geron cloned a different component of telomerase, which it has patented. Geron is already working to develop drugs to combat cancer and aging. Two of the world's leading pharmaceutical companies -- Pharmacia & Upjohn, and Japan's Kyowa Medex -- have signed deals in the past year to pump as much as $88 million in to Geron to develop anti-cancer drugs. Eastman said the company has been working for more than a year to develop a cancer drug that would inhibit telomerase and hope to have one ready for human tests in the next one to three years. Two companies already have licensed Geron's telomerase-detection technology for diagnostic kits for cancer research use and hopes to sign a deal with a large pharmaceutical company to develop diagnostic kits for routine medical use, he said. Posted at 10:04 p.m. PDT Thursday, August 14, 1997