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UAB discovers treatment for brain cancer


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Website: http://www.al.com/news/birminghamnews/index.ssf?/base/news/1122456340256850.xml&coll=2

Posted on: 07/27/2005

UAB discovers treatment for brain cancer

Wednesday, July 27, 2005
DAVE PARKS
News staff writer

A drug used for decades to treat intestinal inflammation may also work against the most common and malignant type of brain tumor, UAB researchers reported Tuesday in the journal Neuroscience.

The finding will give doctors an FDA-approved drug that can be used immediately in an "off label" application to treat desperately ill patients while human trials are conducted, authorities said.

The researchers - led by Harald Sontheimer, director of the Civitan International Research Center at the University of Alabama at Birmingham - found in animal experiments that the drug sulfasalazine stopped or reversed the growth of primary brain tumors known as glioblastoma, a type of cancer that for decades has defied new treatments.

"It had a very profound effect," Sontheimer said in an interview. "We were absolutely stunned."

If it works on humans, the drug would not be a cure, but it could add years to the lives of patients with brain tumors, he said. As it stands now, glioblastoma patients often live only a few months without treatment. Aggressive surgical and radiation treatment can prolong their lives, but usually only by months.

Normally, successful animal experiments signal the beginning of a long, expensive drug development process. But this case is far different, Sontheimer said, because sulfasalazine, sold under the brand name Azulfidinem, has been approved by the Food and Drug Administration and used for decades to treat intestinal inflammation - most notably Crohn's disease - and rheumatoid arthritis.

"We're dealing with a drug already on the shelf," Sontheimer said.

It is a combination sulfa and aspirin drug, and it has been thoroughly tested. Thus, it can move immediately to final human trials - expected to quickly begin through UAB's Brain Tumor SPORE, or Specialized Program of Research Excellence. Sontheimer said the human trial will likely pair the drug with radiation therapy, which is a normal treatment for glioblastoma.

He expects quick results from human trials, likely within two years. There are many questions to answer. First, will the drug really work in humans and how well? Also, the drug is now given orally; would an intravenous or time-released formula work better against brain tumors?

In a prepared release from the journal, Dr. Jeffrey D. Rothstein, director of the Robert Packard Center for ALS Research at Johns Hopkins University, said brain tumors like glioblastoma kill 20,000 Americans a year. "The treatment options are limited - so new research providing therapeutic approaches is very important," he said.

Sulfasalazine appears to attack an "Achilles' heel" that scientists have discovered in brain tumors. It involves a process in which the tumor produces glutathione, a substance that protects cancer cells from toxic byproducts of metabolism.

Scientists have tried for years to stop brain cancer by blocking the synthesis of glutathione but have had little success. Sontheimer said his researchers were working on that problem when they discovered that sulfasalazine interrupted the process. Then, they artificially produced glioblastoma in mice and found that relatively low doses of the drug inhibited or reduced tumor growth.

Sontheimer was the research paper's lead author. Others listed were Wook Joon Chung, Susan A. Lyons, Dr. Gina M. Nelson, Hashir Hamza, Dr. G. Candece L. Gladson and Yancey Gillespie.

UAB researchers have also worked on another drug to treat brain cancer, chlorotoxin. That drug is a synthetic version of a substance derived from scorpion venom and is being tested and developed through a Birmingham company, TransMolecular Inc.

E-mail: dparks@bhamnews.com




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