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Adrenergic receptor b3 (ADRB3)

Studies in patient samples and mice suggest protecting nestin-positive bone marrow mesenchymal stem cells (MSCs) or their neural regulation could be useful for treating myeloproliferative neoplasms (MPNs). In human MPN samples and a mouse model of MPNs, there were decreased numbers of sympathetic nerve fibers that support nestin-positive bone marrow MSCs compared with those in normal samples and mice. In the mouse MPN model, depletion of nestin-positive MSCs accelerated disease progression versus no alteration. In the mouse model, treatment with a neuroprotective agent to prevent loss of sympathetic nerve fibers or an ADRB3 agonist to augment the activity of these fibers improved multiple markers of MPN. Next steps could include developing a method to selectively deliver a small molecule ADRB3 agonist to nestin-positive bone marrow MSCs.
Astellas Pharma Inc. markets the ADRB3 agonist Betanis mirabegron to treat incontinence.
At least three other companies have ADRB3 agonists in Phase II or Phase I testing to treat incontinence or inflammatory bowel disease (IBD).

SciBX 7(28); doi:10.1038/scibx.2014.821
Published online July 24, 2014

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Arranz, L. et al. Nature; published online June 22, 2014;
Contact: Simón Méndez-Ferrer, National Center for Cardiovascular Research, Madrid, Spain