Saturday, December 6, 2008

Antioxidant Fights ALS, Study Finds

Salk Institute scientists have used the first human model of Lou Gehrig's disease built with human embryonic stem cells to determine that a well-known antioxidant in plants fights off the nerve cell death that occurs in the disease.

The antioxidant stopped the oxidation and inflammation that cause the death of the cells, known as motor neurons, according to the work published today in the journal Cell Stem Cell.

The work of the San Diego scientists could aid in the discovery of other molecules that might prevent the neuron death that occurs in the spinal column and usually makes the degenerative disease fatal.

Only one drug, riluzole, has been approved to treat the disease, and that only slows its course by two months, said Fred Gage, the genetics professor who led the study. A variety of drugs that have appeared effective in mouse models of the disease failed to hold up in human trials, Gage said.

“There is an urgent need for new models of the disease that have the potential to translate into clinical trials and that could, at a minimum, be used . . . to verify drugs and drug targets,” Gage said.

Formally known as amyotrophic lateral sclerosis, or ALS, the progressive disease killed baseball Hall of Famer Lou Gehrig in 1941, hence its more commonly used name.

The Salk project began when researcher M. Carol Marchetto decided to try to create a human ALS model using human embryonic stem cells. Scientists have used mouse models, but Gage said that is problematic because ALS is caused by mutations in human genes.

Marchetto created a human model caused by a genetic mutation that impedes the production of the enzyme SOD1, which protects cells from damage caused by free radicals, the highly reactive molecules created during metabolism.

Since that genetic mutation is in every cell, the researchers wanted to look at what might be in the motor neurons' environment, because that is the specific cell killed off in ALS.

The team found that astrocytes, support cells to the motor neurons, were secreting free radicals that cause oxidation and inflammation. Those chemicals were suspected in the motor neuron death, Gage said.

The team then tested for potential drugs that could block the secretion of the free radicals, and hit upon several that looked promising.

The antioxidant apocynin, which is found in many plants, stopped both oxidation and inflammation, protecting the motor neuron from death, according to the journal article.

The team is now testing other molecules for both anti-inflammation and antioxidant properties, Gage said.

Meanwhile, it will use apocynin in mouse models of ALS to see if it helps the animal survive, he said.

Source:
http://www.missouricures.com/site/News2?page=NewsArticle&id=5455&news_iv_ctrl=-1
Margaret Rose Tollerton

Columbia Regional Organizer
Missouri Coalition for Lifesaving Cures
(573) 999.6847 cell
mtollerton@missouricures.com

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