More than 20 years ago, Dr. Lorne Golub of Stony Brook University's School of Dental Medicine began research that would lead to the development of a critical drug—and the only FDA-approved, systematically-administered drug—used in the treatment of periodontal disease, the major cause of tooth loss in the adult population world-wide. Today, at an important conference being held by the American Heart Association in Chicago, important new research was presented indicating that Dr. Golub's original discovery also may have important implications in the treatment of heart disease.
Golub and his colleagues, N. Ramamurthy and Thomas F. McNamara, conducted the research at Stony Brook that led to the discovery of Periostat®, which in 1998 became only the second drug ever developed by a State University of New York institution approved for marketing by the FDA. It has gone on to become the leading treatment in the world for periodontal disease. Now Golub is co-author of a research paper that says this non-antibacterial formulation of a tetracycline—a low-dose doxycycline that is the active ingredient in Periostat®—also lowers c-reactive proteins in the plasma of patients with heart disease. C-reactive protein is a leading diagnostic marker of risk for future heart attacks.
According to the Stony Brook professor, this non-antibacterial tetracycline formulation, or Periostat®, may reduce the risk for heart attack by blocking certain inflammatory mediators, or cytokines, and by inhibiting certain tissue-destructive enzymes or proteinases such as collagenase and gelatinase—the biologically-active chemicals produced by inflammatory and other body cells that can destabilize the fatty plaques in diseased blood vessels. Heart attacks can result when pieces of these plaques float downstream, blocking smaller blood vessels leading to the heart and other organs.
Some of these findings were presented today at the AHA's Scientific Sessions 2002 by Dr. David Brown, Director of Interventional Cardiology and the Cardiac Catheterization Laboratories at Beth Israel Medical Center in New York. Researchers presenting at Scientific Sessions provide reveal recent leading advances in the diagnosis and treatment of cardiovascular disease and stroke, as well as clinical research advances. Dr. Golub also attended the event as co-author of this scientific paper.
"Tetracyclines have been in use as antibiotics for around 50 years," Golub said. "But even after all that time, our research revealed unexpected new properties for this old family of drugs. To find new uses for drugs that can have profound impact on the treatment of a wide variety of diseases has been a long and exciting journey."
Golub believes that the ability of tetracyclines to inhibit these tissue-destructive enzymes, which are produced in excessive amounts by diseased tissues, may be useful in the fight against other diseases including arthritis, diabetes, osteoporosis, and even cancer. Recent clinical trials by his team and other institutions are providing evidence for their optimism.
Back in the late 1970s, Golub and his team learned that gingival tissue in diabetic rats produced markedly elevated activity of collagenase—the enzyme that breaks down collagen. By treating the rats with a semi-synthetic tetracycline, the Golub team's objective was to suppress the oral bacteria. But what they later found would go on to revolutionize the treatment of periodontal disease—and potentially many other diseases.
Golub is considered one of the leading dental researchers in the country. He has been funded by the National Institute of Dental Research (NIDCR/NIH) since 1974 and new NIH grants are funding his studies through 2005. He has received numerous honors for his work, including an NIH Merit Award. He also was the 1998 recipient of the research award in Oral Biology at the annual meeting of the International Association for Dental Research in Nice, France, and was named the winner of the American Dental Association's 2001 Norton M. Ross Award for Excellence in Clinical Research.
Dr. Golub has published over 220 original articles and has been issued 32 patents. He joined the Stony Brook faculty in 1973.
