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Toxin and Potential MS Treatment Focus of Research

11/24/2010

Researchers from Purdue University in Indiana have found evidence that an environmental pollutant may play an important role in causing MS, and that a hypertension drug might be used to treat the disease.

The toxin acrolein was elevated by about 60 percent in the spinal cord tissues of mice with a disease similar to MS, said Riyi Shi, a medical doctor and a professor of neuroscience and biomedical engineering in Purdue’s Department of Basic Medical Sciences, School of Veterinary Medicine, Center for Paralysis Research and Weldon School of Biomedical Engineering.

The compound is an environmental toxin found in air pollutants including tobacco smoke and auto exhaust. Also, acrolein is produced within the body after nerve cells are damaged. Acrolein induces the production of free radicals, compounds that cause additional injury to tissues after disease or physical trauma.

Previous studies by this research team found that neuronal death caused by acrolein can be prevented by administering the drug hydralazine, an FDA-approved medication used to treat hypertension. The elevated acrolein levels in the MS mice were cut in half when treated with hydralazine.

"Only recently have researchers started to understand the details about what acrolein does to the human body," Shi said. "We are studying its effects on the central nervous system, both in trauma and degenerative diseases such as multiple sclerosis."

The new findings show that hydralazine also delays onset of the MS-like disease in mice and reduces the severity of symptoms by neutralizing acrolein.

"The treatment did not cause any serious side effects in the mice," Shi said. "The dosage we used for hydralazine in animals is several times lower than the standard dosing for oral hydralazine in human pediatric patients. Therefore, considering the effectiveness of hydralazine at binding acrolein at such low concentrations, we expect that our study will lead to the development of new neuroprotective therapies for MS that could be rapidly translated into the clinic."

The researchers also learned the specific chemical signature of the drug that binds to acrolein and neutralizes it, potentially making it possible to create synthetic alternatives with reduced side effects. The studies are detailed in a paper appearing online this month in the journal Neuroscience.

"We think that acrolein is what degrades myelin, so if we can block that effect then we can delay the onset of MS and lessen the symptoms," Shi said.

Other researchers had previously shown that acrolein damages liver cells and that the damage can be alleviated by hydralazine, leading the Purdue researchers to study its possible effects on spinal cord tissues.

Further research will be conducted, and Shi's group has identified other potential compounds for binding acrolein.

 



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