\ ALS Research \ Celebrex Works Well In ALS Mouse Models
A commonly-used drug for arthritis may be of benefit to ALS patients, if first-stage animal studies are any sign. In an article in this month's Annals of Neurology, scientists with Johns Hopkins and with the Robert Packard Center for ALS Research at Johns Hopkins report that the drug Celebrex significantly delayed the onset of weakness and weight loss in mouse models of the disease. As important, the drug increased the animals' life span by 25 percent.
"We've also shown that, at this dosage, Celebrex does its work in precisely the place you'd want it to: in the animals' spinal cords and brains," says Packard Center director, Jeffrey Rothstein, M.D., Ph.D., senior author of the report. In the near future, adds Daniel Drachman, M.D., who led the research team, "We hope it may become part of a new, multi-therapy approach to the disease in humans."
Whether used for human arthritis or for ALS, the principle behind Celebrex is the same: it inhibits a key enzyme, called COX-2, that's part of the body's inflammatory and other pathways.
In ALS, three destructive processes play a strong part in the downward spiral of patients' motor neurons. The first, excitotoxicity, refers to an excess of the nerve transmitter glutamate, which overstimulates neurons, causing harm. The second is the production of toxic free radical molecules and the third is inflammation. The inspiration for the study came when Drachman realized Celebrex could, in theory, damp down all three.
The researchers gave Celebrex-laced chow to mouse models of ALS and followed their progress by monitoring motor function, weight and general activity. At intervals, the scientists also examined and analyzed animal tissues, comparing the drug-fed mice with model mice that didn't get Celebrex. "The treated mice had a notable delay in symptom onset," says Rothstein, "and lived significantly longer as well." No human treatment, so far, has extended life span as dramatically as did Celebrex in the model mice.
"The availability of potent COX-2 inhibitors that readily reach target tissues and that are generally safe to take has led us to undertake a multicenter human trial," says Drachman, "using high-doses in ALS patients."
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The Robert Packard Center for ALS Research at Johns Hopkins is a collaborative effort by some of the best ALS and non-ALS scientists to aggressively and rapidly develop new treatments and find a cure for ALS, also known as Lou Gehrig's disease. It's the only institution of its kind dedicated solely to the disease. Research conducted by the Center is meant to translate from bench to bedside in an expedited time frame. Center scientists from institutions around the world have made some of the most important discoveries in ALS, leading to advances in understanding and treatment of the disease.
The nature of ALS shapes the Center's aggressive, results-oriented scientific approach. ALS is a devastating, progressive neuromuscular disease that causes complete paralysis and loss of function – including the ability to eat, speak and breathe -- and eventually, death. ALS progresses quickly and is not curable. Most patients die within five years of diagnosis.
To learn more about The Robert Packard Center for ALS Research at Johns Hopkins, including the latest information on ALS research and treatment, log on to www.alscenter.org
Information from:
Johns Hopkins ALS News Network
December 18, 2002
Source: Johns Hopkins
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Celebrex Works Well In ALS Mouse Models
A commonly-used drug for arthritis may be of benefit to ALS patients, if first-stage animal studies are any sign. In an article in this month's Annals of Neurology, scientists with Johns Hopkins and with the Robert Packard Center for ALS Research at Johns Hopkins report that the drug Celebrex significantly delayed the onset of weakness and weight loss in mouse models of the disease. As important, the drug increased the animals' life span by 25 percent.
"We've also shown that, at this dosage, Celebrex does its work in precisely the place you'd want it to: in the animals' spinal cords and brains," says Packard Center director, Jeffrey Rothstein, M.D., Ph.D., senior author of the report. In the near future, adds Daniel Drachman, M.D., who led the research team, "We hope it may become part of a new, multi-therapy approach to the disease in humans."
Whether used for human arthritis or for ALS, the principle behind Celebrex is the same: it inhibits a key enzyme, called COX-2, that's part of the body's inflammatory and other pathways.
In ALS, three destructive processes play a strong part in the downward spiral of patients' motor neurons. The first, excitotoxicity, refers to an excess of the nerve transmitter glutamate, which overstimulates neurons, causing harm. The second is the production of toxic free radical molecules and the third is inflammation. The inspiration for the study came when Drachman realized Celebrex could, in theory, damp down all three.
The researchers gave Celebrex-laced chow to mouse models of ALS and followed their progress by monitoring motor function, weight and general activity. At intervals, the scientists also examined and analyzed animal tissues, comparing the drug-fed mice with model mice that didn't get Celebrex. "The treated mice had a notable delay in symptom onset," says Rothstein, "and lived significantly longer as well." No human treatment, so far, has extended life span as dramatically as did Celebrex in the model mice.
"The availability of potent COX-2 inhibitors that readily reach target tissues and that are generally safe to take has led us to undertake a multicenter human trial," says Drachman, "using high-doses in ALS patients."
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
The Robert Packard Center for ALS Research at Johns Hopkins is a collaborative effort by some of the best ALS and non-ALS scientists to aggressively and rapidly develop new treatments and find a cure for ALS, also known as Lou Gehrig's disease. It's the only institution of its kind dedicated solely to the disease. Research conducted by the Center is meant to translate from bench to bedside in an expedited time frame. Center scientists from institutions around the world have made some of the most important discoveries in ALS, leading to advances in understanding and treatment of the disease.
The nature of ALS shapes the Center's aggressive, results-oriented scientific approach. ALS is a devastating, progressive neuromuscular disease that causes complete paralysis and loss of function – including the ability to eat, speak and breathe -- and eventually, death. ALS progresses quickly and is not curable. Most patients die within five years of diagnosis.
To learn more about The Robert Packard Center for ALS Research at Johns Hopkins, including the latest information on ALS research and treatment, log on to www.alscenter.org
Information from:
Johns Hopkins ALS News Network
December 18, 2002
Source: Johns Hopkins
| Posted On: Friday, December 20, 2002 Modified: Friday, December 20, 2002 Category: ALS Research Posted By: |