Research shows inflammation link between two disorders
MONDAY, Aug. 17 (HealthDay News) -- Dr. Lawrence Steinman has this seemingly crazy idea that a drug commonly used to combat high blood pressure can help prevent the damage done to nerve cells in multiple sclerosis.
But people in the know tend to listen carefully to the ideas of Steinman, a professor of neurology at Stanford University, because one of his ideas was crucial in the development of natalizumab (Tysabri), a now widely used medication that can reduce the incidence of relapses in multiple sclerosis (MS) by two-thirds.
Research exploring Steinman's latest brainstorm appears online Aug. 17 in the Proceedings of the National Academy of Sciences.
Steinman said he got his latest idea after he was prescribed the ACE inhibitor lisinopril (Zestril) for high blood pressure. When he put the drug name into his computer's search engines, vague references to a relationship between the drug's target, angiotensin, and multiple sclerosis started showing up.
An ACE (angiotensin-converting enzyme) inhibitor blocks the activity of an enzyme that converts angiotensin to a form that tightens blood vessels.
"Angiotensin constricts blood vessels in response to standing up, so we don't faint," he said. "Nerve cells are intrinsically tied up with blood vessel walls, and that pathway plays a role in inflammation."
Inflammation also plays a crucial role in multiple sclerosis, in which the body's immune system attacks the myelin sheath of nerve cells in the brain. "We can also argue that inflammation plays a role in hypertension," Steinman said.
Working with researchers from other institutions, he put the idea to a variety of tests, such as examining tissue from brain samples of people with MS. The studies showed significantly elevated levels of the cell receptors for angiotensin and the enzyme blocked by lisinopril and other ACE inhibitors.
But surely, an effect on MS of such widely used drugs should have been noticed by now? Not so sure, Steinman said. "Generally, one doesn't start taking an ACE inhibitor until about age 60," he said. "Multiple sclerosis is a disease that starts in early adulthood, so not many people in the early stages of MS are taking an ACE inhibitor."
Steinman would like to go directly to a human trial to test his proposal, but there are practical difficulties. "Who's going to pay for it?" he asked. A standard proof-of-concept study with about 200 patients would cost in the vicinity of $20 million. ACE inhibitors are as inexpensive as any prescription drug at this time, so pharmaceutical companies won't see any profits from financing a study, he said.
Steinman said he plans to apply to the U.S. National Institute of Neurological Disorders and Stroke for funding, but he acknowledges that "in general, NINDS doesn't have that kind of money."
In the meantime, basic research will continue, he said. "We are seeing the type of nerve cells that angiotensin reacts with, the mediators that are reducing inflammation," Steinman said. "This is an unexpected pathway of inflammation in MS."
"It's a very interesting proposal," said Patricia O'Looney, director of biomedical research at the National Multiple Sclerosis Society, which has financed some of the research. "The interest in MS is to find new strategies in order to control inflammation, what is the best way to control the pro-inflammatory molecules in MS."
There was some interest in studying the role of angiotensin in MS years ago, "but we didn't know much about the immune system 10 or 15 years ago," O'Looney said. "Now we can use state-of-the-art technology to examine the expression of proteins in human tissue. There could be a role of angiotensin in this inflammatory pathway. Perhaps by controlling these pathways we can actually shift the immune balance in a favorable way."
All the aspects of MS are explored by the National Multiple Sclerosis Society.
SOURCES: Lawrence Steinman, M.D., professor, neurology, Stanford University, Stanford, Calif.; Patricia O'Looney, Ph.D., director, biomedical research, National Multiple Sclerosis Society, New York City; Aug. 17, 2009, Proceedings of the National Academy of Sciences, online
All rights reserved