**Review of Pharmacological Strategies with Repurposed Drugs for Hereditary Hemorrhagic Telangiectasia Related Bleeding**

**Virginia Albiñana 1,2, Angel M. Cuesta 1,2, Isabel de Rojas-P 1, Eunate Gallardo-Vara 3, Lucía Recio-Poveda 1,2, Carmelo Bernabéu 1,2 and Luisa María Botella 1,2,\***



Received: 24 April 2020; Accepted: 3 June 2020; Published: 6 June 2020

**Abstract:** The diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria: epistaxis, telangiectases, arteriovenous malformations in internal organs, and family history. Genetically speaking, more than 90% of HHT patients show mutations in *ENG* or *ACVRL1*/*ALK1* genes, both belonging to the TGF-β/BMP9 signaling pathway. Despite clear knowledge of the symptoms and genes of the disease, we still lack a definite cure for HHT, having just palliative measures and pharmacological trials. Among the former, two strategies are: intervention at "ground zero" to minimize by iron and blood transfusions in order to counteract anemia. Among the later, along the last 15 years, three di fferent strategies have been tested: (1) To favor coagulation with antifibrinolytic agents (tranexamic acid); (2) to increase transcription of *ENG* and *ALK1* with specific estrogen-receptor modulators (bazedoxifene or raloxifene), antioxidants (N-acetylcysteine, resveratrol), or immunosuppressants (tacrolimus); and (3) to impair the abnormal angiogenic process with antibodies (bevacizumab) or blocking drugs like etamsylate, and propranolol. This manuscript reviews the main strategies and sums up the clinical trials developed with drugs alleviating HHT.

**Keywords:** HHT; ALK1; endoglin; raloxifene; bazedoxifene; tranexamic acid; propranolol; FK506; etamsylate; N-acetylcysteine
