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Unlocking the Potential
CHORI Scientists Identify Novel Anti-Oxidant with for Treating Oxidative Stress Due to Iron Overload

"We found that alpha-lipoic acid has significant anti-oxidant activity that is further enhanced by acetyl-L-carn-itine. The com-bination of the two could be a very effective way to reduce oxidative stress."

CHORI scientist Ashutosh Lal, in collaboration with Bruce Ames, PhD, and his other colleagues in CHORI’s Center for Nutrition & Metabolism, has just published in the March issue of Redox Report evidence of a novel and highly potent anti-oxidant that could be the key to reducing oxidative stress due to iron overload in patients with chronic anemias such as sickle cell disease (SCD) and thalassemia.

“We looked at a novel group of anti-oxidants to see which might be the most effective against oxidative stress caused by iron overload,” says Dr. Lal.

Iron overload is a common problem in disorders like SCD and thalassemia, due to the regular blood transfusions that are required to treat the conditions. The oxidative stress that results can cause significant and sometimes fatal complications, such as organ injury, endocrinopathies, diabetes, and heart failure, which is why researchers have long been pursuing the possibility of an effective anti-oxidant therapy.

Several possible anti-oxidants, such as vitamin E, have been tested in the past, but with little clinical effect. Alpha-lipoic acid (LA), enhanced with acetyl-L-carnitine (ALCAR), may just be the answer researchers have been looking for.

"There are two reasons why LA may prove more effective than the others," Dr. Lal. explains.

"One is the potency - LA is much more potent than several of the conventional anti-oxidants and works in a variety of cellular environments. The second reason is that LA induces activity of phase 2 enzymes that are involved in cellular protection. This causes improvement in glutathione content, which in turn makes the cells more resistant to oxidative stress."

Based on the strength of the results in this Redox Report study, Dr. Lal and his colleagues have already conducted a pilot study of the new anti-oxidant combination in SCD patients. While the results of the pilot study won't be published until the next 3 to 4 months, they provided enough substantive data for Dr. Lal and his colleagues to garner National Institutes of Health funding to pursue a phase 1 clinical trials as soon as FDA approval comes through.

“The clinical trials are very important,” says Dr. Lal. “We need to translate the lab results into human trials to confirm that this new combination, which has such a high degree of potency, will prove clinically effective.”

Given LA’s high potency and broad antioxidant properties, Dr. Lal hopes to have finally found the key to unlocking the potential of anti-oxidant therapy.

“We believe that where there is oxidative stress which has arisen in response to iron accumulation in the body, that we may have found a novel combination of anti-oxidants that can actually influence the severity of the complications in sickle cell and thalassemia patients,” says Dr. Lal.

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Tuesday, May 17, 2011 8:19 AM

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