Lisinopril hypertension drug could be helpful for multiple sclerosis
Posted Dec 10 2009 5:02pm
Researchers at the Stanford University School of Medicine found a drug used to treat high blood pressure, lisinopril, an inexpensive drug with a proven safety track record, may have therapeutic benefit for multiple sclerosis as well.
Amazingly, the study began seven years ago when Dr. Lawrence Steinman M.D, senior author of the study and neurology professor, had a problem with his home computer. Dr. Steinman is a famous multiple sclerosis researcher who has earlier work with the inflammatory appearance of the disease. His work sparked development of a tremendous class of anti-inflammatory multiple sclerosis therapies that included a drug called natalizemab that is marketed under the trade name Tysabri.
Dr. Steinman had been seeing another doctor about his high blood pressure and had been given a prescription for lisinopril, and, wanting to know more about it, he typed in the name of the drug in his search engine. The computer would naturally insert the additional phrase “multiple sclerosis”, a problem that had been ongoing but he had not fixed.
Since the additional phrase “multiple sclerosis” was inserted into his search field, a list of medical links revealed interesting hints of a possible connection between multiple sclerosis and a hormone, angiotensin, whose receptors are all over blood-vessel walls throughout the body. Overactive angiotensin is a component of hypertension and, seeing this possible link, interested Dr. Steinman enough that he wanted to go further with it.
Dr. Steinman and his colleagues tested the theory in different ways starting with examining multiple sclerosis lesions of brain samples from autopsied patients.
Next, they turned to a laboratory-bred type of mouse that was immunized with a certain chemical that caused the mice to develop brain lesions quite similar to lesions that have been seen in multiple sclerosis. When the mice were given the disease triggered chemical and then injected with the lisinopril, with doses that were equal to those prescribed for humans with high blood pressure, the mice didn’t develop the paralysis that is characteristic of multiple sclerosis progression. And on the other side, when the mice were given the lisinopril after
Another observation by the team was that lisinopril reduced many molecular inflammations that follow multiple sclerosis in humans and the animal model and that it, more importantly, did not hurt or constrain the mice’s overall immune proficiency.
Interestingly enough, Dr. Steinman and his team also saw the lisinopril trigger an important class of immune cells called regulatory T cells. T cells stop autoimmune diseases by holding up the activity of other immune cells that mistakenly strike at cells and tissues that should be left alone. “It’s likely that this proliferation was a key component in the protection provided by the drug,” Dr. Steinman said, “as an infusion of regulatory T cells from mice that had been given lisinopril was sufficient to prevent or reverse the disease process in mice that have been given none.”
Marc Feldmann, an Imperial College London immunologist who has known of the study but did not contribute is quoted as saying, “Steinman’s results have major public-health implications. If multiple sclerosis patients can be treated with lisinopril at something like 1 percent of the price of treatment with Tysabri, then far more patients will receive adequate therapy, at a substantially lower cost to those paying for it.”
First authorship of the paper is shared by two postdoctoral researchers in Steinman's lab: Michael Platten, MD, and Sawsan Youssef, PhD. (Platten is now a neurology professor at University Hospital of Heidelberg, in Germany.) Other Stanford co-authors include May Han, MD, acting assistant professor of neurology and neurological sciences, and Raymond Sobel, MD, professor of pathology.
The study was financed by the National Institutes of Health, the National MS Society, the Phil N. Allen Trust, the German Research Foundation, the Helmholtz Association, the U.S. Public Health Service and the Biomedical Sciences Exchange Program.
The Stanford University School of Medicine consistently ranks among the nation's top 10 medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html. Molecular detection methods turned up elevated levels of both the angiotensin receptor and the angiotensin-producing enzyme blocked by lisinopril. they had developed full-blown symptoms, it was seen to have reversed their paralysis.