[ad_1]
The discovery of a new target for propranolol, a drug for hypertension, could lead to the development of new, safer treatments for vascular diseases, according to new findings published in eLife.
The study also helps explain how propranolol is able to reduce benign tumors in infants called hemangiomas and relieve symptoms in some individuals born with a rare condition called hypotrichosis-lymphedema-telangiectasia and renal syndrome ( HLTRS), which causes a proliferation of blood vessels.
The ability of propranolol to block adrenaline receptors has made it a mainstay of treatment for hypertension and other heart conditions for decades. More recently, the drug has been reused to treat hemangiomas, although it is unclear exactly how it is able to reduce tumors. But then, a teenage patient with unusually mild symptoms of HLTRS, caused by mutations of a gene called SOX18, was found. The patient was taking high doses of propranolol from a young age to control her hypertension.
"The milder symptoms observed in this patient with HLTRS taking propranolol raised the possibility that the drug has a SOX18-dependent molecular mode of action in addition to its beta-blocking activity," states the author Co-Principal Jeroen Overman, PhD student at the Institute. for Molecular Bioscience, University of Queensland, Australia.
When a 17-month-old patient in Dubai, with HLTRS and a SOX18 mutation, developed heart problems, his doctors and parents chose to try propranolol. This treatment quickly resolved the child's heart problem, reinforcing the idea that the drug was targeting SOX18.
The team conducted experiments on laboratory-grown cells and confirmed that propranolol directly interferes with SOX18 activity by preventing it from binding to other SOX18 proteins. Subsequent studies in mice, in which researchers treated eight-day-old mice with SOX18 mutations with propranolol, revealed that the drug eliminated the proliferation of HLTRS-like blood vessels in the cornea usually seen in mice with these mutations.
Finally, a collaborative team from the Boston Children's Hospital, led by co-lead author Joyce Bischoff, treated hemangioma cells taken from patients and cultured in the laboratory with propranolol. They discovered that the blocking action of the drug SOX18 stopped the differentiation of tumor cells. Specifically, they showed that a component of propranolol, the enantiomer R (+), was responsible for the SOX18 blocking effect, while its mirror image, the S enantiomer (-), was only a weak effect.
"This finding suggests that it would be possible to treat hemangiomas or HLTRS using only the R (+) enantiomer of propranolol," says co-lead author Mathias Francois, PhD, badociate professor at The Institute of Molecular Bioscience at the University of Queensland. "This would allow lower doses of the drug or shorter duration of treatment, while sparing patients the potential side effects badociated with beta-blockers."
In addition to opening the door to improved hemangioma treatment or HLTRS, this discovery could lead to the development of new treatments for other conditions involving excessive growth of blood vessel cells. "Our work could potentially reuse the R (+) enantiomer of propranolol as a treatment for a wide range of conditions including vascular disorders," concludes Joyce Bischoff, PhD student, Senior Researcher, Vascular Biology Program. and professor in the Department of Vascular Biology. Surgery at Boston Children's Hospital and Harvard Medical School, Boston, USA.
Source of the story:
Material provided by eLife. Note: Content can be changed for style and length.
Source link
