Antihypertensive drugs, using a new signalling pathway of brain cells, could control inflammation in multiple sclerosis (MS), say researchers in Heidelberg and Stanford.
The peptide angiotensin not only raises blood pressure but also activates the immunological messenger substance TGF beta on a previously unknown communication pathway in the brain, found study conducted by Stanford Professor Lawrence Steinman along with Heidelberg's Dr. Tobias Lanz and Dr. Michael Platten.
Angiotensin II is known as a molecule that regulates blood pressure.
These are immune cells that are involved in autoimmune reactions and chronic-inflammatory diseases such as MS.
MS is characterized by multifocal areas of inflammation in the brain and spinal cord that lead to paralysis and other neurological symptoms.
The scientists working with Professor Platten showed in a mouse model that angiotensin II promotes inflammation in the brain and spinal cord.
When the angiotensin receptors, i.e. the sites where angiotensin docks onto cells and can develop its effect, were blocked by the orally administered blood pressure drug Candesartan, the inflammation decreased and the paralysis resolved.
"Since AT1R blockers are frequently prescribed for lowering blood pressure and have a proven safety profile, it is an obvious step to test them soon in MS patients. Of course, in research it is important to search for specific drugs with new molecular targets. But in our study, we show that approved medications can also be successfully studied for benefits in other diseases. The potential use of these generic drugs with a proven safety profile would also have a great impact on reducing healthcare costs," said Platten.
The researchers know that angiotensin transfers its information to the cell via an increase in the messenger substance Transforming Growth Factor beta (TGF beta).
Such a "network pathway" between angiotensin and TGF beta was previously unknown in the brain. TGF beta can have completely opposite effects - on the one hand it regulates and alleviates inflammatory reactions, but in other situations it causes inflammation and promotes it.
Which function the factor has depends on the surrounding tissue and the interaction with other messenger substances.
With respect to the whole body, TGF beta appears to protect the organism from inflammation and autoimmune diseases.
However, paradoxically, blockage of TGF beta production in the brain leads to a reduction of inflammation and thus to an improvement in symptoms.
"AT1R blockers prevent only the peak concentrations of TGF beta in the brain triggered by angiotensin, which are responsible for the inflammatory reaction. The baseline levels of TGF beta are not affected, so that the protective function for the rest of the body is apparently sustained," explained Platten.
The study is published in the "Journal of Clinical Investigation".