Tuesday, May 30, 2023

U research plays part in better drug development

September 28, 2000

Aspirin’s been a staple item in backpacks, purses and medicine cabinets for years, and is said to reduce the risk of heart attacks and ease pain.

But 15 years of research by MSU scientists has led to a better understanding of a crucial protein - prostaglandin endoperoxide synthase 1, or PGHS-1 - targeted by aspirin and other anti-inflammatory drugs such as ibuprofen and naproxen.

Armed with understanding of how these drugs interact with PGHS-1, scientists may be able to develop drugs that better target specific diseases.

The research, conducted by William Smith, chairperson of the Department of Biochemistry and Molecular Biology, and Michael Garavito, professor of biochemistry and molecular biology, is detailed in the Sept. 15 issue of the journal “Science.”

Aspirin and other NSIADs - non-steroidal anti-inflammatory drugs - also react with PGHS-1’s nearly identical twin, PGHS-2.

“When you take an aspirin, that’s what the aspirin attacks,” Garavito said. “Aspirin targets these two enzymes, PGHS-1 and PGHS-2, and turns them off.”

By finding the subtle differences between the two proteins, researchers may be able to develop other drugs more beneficial to those suffering from chronic pain, specifically osteoarthritis.

The reaction between the drug and the proteins is what stops the pain, swelling, high blood pressure and other ailments aspirin relieves - but can also irritate the user’s stomach lining.

“When you’re very sensitive to aspirin you run the risk of gastrointestinal bleeding,” Garavito said. “That’s why people are looking for better alternatives.”

Celebrex and Vioxx, developed by competing pharmaceutical companies, don’t affect stomach lining like aspirin, by leaving PGHS-1 alone. The drugs were approved by the FDA last year.

MSU research played a role in the development of these drugs.

“Let’s say that both companies have used the information from our research in their development of Vioxx and Celebrex,” Garavito said. “We did contribute, not in a huge, but a significant way.”

Dana Beaman, chief pharmacist at the Clinical Center, said he has been filling a steady flow of prescriptions for Celebrex and Vioxx, mostly for those afflicted with osteoarthritis.

But the new drugs didn’t come without a cost.

“They complain about price,” Beaman said. “These are very costly medications compared to NSIADs that are available. As far as the side-effect profile goes we really haven’t been getting any complaints.”


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