The Role of Propranolol as a Repurposed Drug in Rare Vascular Diseases

Abstract

Rare Diseases (RD) are defined by their prevalence in less than 5 in 10,000 of the general population. Considered individually, each RD may seem insignificant, but together they add up to more than 7000 different diseases. Research in RD is not attractive for pharmaceutical companies since it is unlikely to recover development costs for medicines aimed to small numbers of patients. Since most of these diseases are life threatening, this fact underscores the urgent need for treatments. Drug repurposing consists of identifying new uses for approved drugs outside the scope of the original medical indication. It is an alternative option in drug development and represents a viable and risk-managed strategy to develop for RDs. In 2008, the “off label” therapeutic benefits of propranolol were described in the benign tumor Infantile Hemangioma. Propranolol, initially prescribed for high blood pressure, irregular heart rate, essential tremor, and anxiety, has, in the last decade, shown increasing evidence of its antiangiogenic, pro-apoptotic, vasoconstrictor and anti-inflammatory properties in different RDs, including vascular or oncological pathologies. This review highlights the finished and ongoing trials in which propranolol has arisen as a good repurposing drug for improving the health condition in RDs.

Experimental approaches for altering the expression of Abeta‐degrading enzymes

“…The β-adrenergic antagonist propranolol also increased IDE levels in an AD mouse model (Dobarro et al, 2013). Propanolol is used to treat hypertension, arrhythmias, essential tremor, and anxiety (Cuesta et al, 2022) and has been used…”

“…The β‐adrenergic antagonist propranolol also increased IDE levels in an AD mouse model (Dobarro et al, 2013). Propanolol is used to treat hypertension, arrhythmias, essential tremor, and anxiety (Cuesta et al, 2022) and has been used to reduce disruptive behaviors in patients with AD and other dementias (Pauszek, 1991; Peskind et al, 2005; Shankle et al, 1995; Weiler et al, 1988). Also of relevance to AD, propranolol was recently found to have acetylcholinesterase‐inhibiting activity (Ciprés‐Flores et al, 2020).…”

VEGF Pathway Gene Expression Profile of Proliferating versus Involuting Infantile Hemangiomas: Preliminary Evidence and Review of the Literature

“…Despite the long use of propranolol mainly as a therapy for proliferating hemangioma, its action and efficiency are still questionable. Mulliken discovered that propranolol acts differently on different cell types based on hemangioma structure using histochemical methods [ 24 ], and Glowacki observed hemangioma cell heterogeneity in hemangioma cells. Hemangioma-derived progenitor/stem cells (HemSCs), mesenchymal stem cells (Hem-MSCs), endothelial progenitor cells (HemEPCs), endothelial cells (HemECs), and perivascular cells (Hem-pericytes) have all been isolated from hemangioma tissues in recent decades [ 25 , 26 , 27 , 28 ].…”

Beta-blockers in cardiac arrhythmias–Clinical pharmacologist’s point of view

“…All these mechanisms contributed to the successful use of propranolol in the treatment of infantile hemangiomas (IH) ( You et al, 2021 ; Cuesta et al, 2022 ). It has been shown that this indication is more effective than steroids, although patients treated with propranolol should be monitored due to the risk of recurrence and the possible need for re-treatment ( Frongia et al, 2021 ; You et al, 2021 ).…”