Blood pressure drug reverses MS symptoms in mice
A widely used blood pressure drug may hold promise as a treatment for multiple sclerosis, U.S. researchers said on Monday.
Lab tests found the generic drug lisinopril, developed by Merck and sold as Prinivil or Tensopril, prevented paralysis in mice with a form of MS.
Lisinopril was quite powerful, and could even reverse paralytic disease (in mice), said Dr Lawrence Steinman of Stanford University School of Medicine in California, whose study appears in the Proceedings of the National Academy of Sciences.
Lisinopril, also sold by AstraZeneca as Zestril, is an angiotensin-converting enzyme, or ACE inhibitor. It acts by blocking angiotensin, a hormone that makes blood vessels contract, increasing blood pressure.
The angiotensin system is critical for maintaining blood pressure, but it may play other roles, Steinman said in an e-mail. He said angiotensin is directly related to a biochemical mechanism called nuclear factor kappa B, or NF-kB, which underlies inflammation.
MS occurs when the immune system mistakenly attacks the myelin sheath protecting nerve cells, disrupting communication between the brain and other parts of the body. It affects about 2.5 million people globally, producing symptoms that range from mild illness to permanent disability.
Since both MS and high blood pressure are diseases caused in part by inflammation, Steinman and colleagues wanted to see if angiotensin was involved in the autoimmune disease.
Steinman's earlier work on inflammation in MS helped lay the groundwork for the blockbuster drug natalizumab or Tysabri, sold by Biogen Idec and Elan Corp.
For the latest research, Steinman's team studied brain tissue from patients with MS. They found elevated levels of receptors -- molecular doorways in cells -- for angiotensin. They also found more receptors for the enzyme that is blocked by the drug lisinopril.
The receptors were on blood vessels but also on neurons and surrounding brain cells, Steinman said.
The researchers studied the effects of the drug using mice injected with a chemical that causes them to develop MS-like symptoms.
The team gave lisinopril to healthy mice, then gave the injection that triggers the MS-like disease. Mice that got lisinopril first did not develop MS.
Mice that had been injected with lisinopril had an abundance of immune system cells known as regulatory T cells that are capable of damping down the immune system.
When they transferred regulatory T cells from mice exposed to lisinopril into a paralyzed mouse, they quickly reversed paralysis, Steinman said.
Steinman said the finding suggests the same effect might occur in people with MS, and possibly other autoimmune diseases.
It will be important to test whether lisinopril and other angiotensin blockers can do this in MS patients, he said. We are trying to secure funds to run such trials beginning next year.