Beta blockers can repair defective blood vessels in the brain

PICTURE: Propranolol treatment contributes to the reduction of the number and size of cerebral cavernous malformations. Panel A shows a brain section of a vehicle-treated mouse. The lesions are marked in green. view more

Credit: Joppe Oldenburg

Review / experimental study / Animals

Propranolol, a drug that is effective against pediatric hemangiomas (“strawberry naevi,” similar to birthmarks), can also be used to treat cerebral cavernous malformations, conditions characterized by poorly formed blood vessels in the brain and elsewhere. This was shown by researchers from Uppsala University in a new study published in a scientific journal Stroke.

“So far, there has been no drug treatment for these patients, so our results could become extremely important to them,” says Peetra Magnusson of the University’s Department of Immunology, Genetics and Pathology, who led the study.

Cerebral cavernous malformations (CCM, cavernous angiomas, or cavernomas) are vascular lesions on blood vessels in the brain and elsewhere, caused by genetic changes that may be inherited or occur spontaneously. Today, surgery to remove these lesions is the only possible treatment. However, surgical interventions in the brain are very risky. Because, in addition, vascular malformations recur in a hereditary form, treatment of CCM is urgently needed.

The use of propranolol, a beta blocker, includes the treatment of cardiovascular diseases and conditions, such as high blood pressure. But it can also be used to treat hemangiomas (“strawberry naevus”), a common malformation of blood vessels in children. There are some indications that the preparation could also work against CCM.

The new study is a collaboration between researchers from Uppsala University, the Swedish University of Agricultural Sciences and, in Italy, IFOM – the Institute of Molecular Oncology FIRC and the Mario Negri Institute of Pharmacological Research. Researchers are investigating how propranolol affects the appearance of vascular lesions in the form of CCM.

“We tested mice with vascular malformations in the brain – cavernomas or CCMs, as they are called – that corresponded to the hereditary form of the condition in humans. The mice were given propranolol in drinking water and we could see that the cavernomas were getting smaller and smaller. Blood vessels also functioned better, with fewer leaks and improved contacts between their cells, ”says Magnusson.

The dose of propranolol administered to the animals was equivalent to the dose used to treat the disease in humans. Using an electron microscope, the researchers were able to study in detail how the drug affected the cavernoma.

The results indicate that propranolol can be used to reduce and stabilize vascular lesions and may be a potential drug for the treatment of CCM.

“What makes this study particularly interesting is that a clinical study is currently underway in Italy in which patients with CCM will receive two years of propranolol treatment. During that period, they are monitored by magnetic resonance imaging of blood vessels to see how malformations develop.” , says Professor Elisabetta Dejana from the Department of Immunology, Genetics and Pathology at Uppsala University and IFOM in Italy.

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Dejana is at the head of a research group at Uppsala University that is working on a new study, and is also participating in an ongoing clinical study in Italy.

Oldenburg. J. et all. (2021), Propranolol reduces the development of lesions and saves barrier function in cerebral-cavernous malformations, Stroke.DOI: 10.1161 / STROKEAHA.120.029676

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