Review of Pharmacological Strategies with Repurposed Drugs for Hereditary Hemorrhagic Telangiectasia Related Bleeding
Open Access
- 5 June 2020
- journal article
- review article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 9 (6), 1766
- https://doi.org/10.3390/jcm9061766
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 different 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.Funding Information
- Instituto de Salud Carlos III (CIBERER U 707)
This publication has 99 references indexed in Scilit:
- Topical timolol for the treatment of epistaxis in hereditary hemorrhagic telangiectasiaAmerican Journal of Otolaryngology, 2012
- Propranolol as antiangiogenic candidate for the therapy of hereditary haemorrhagic telangiectasiaThrombosis and Haemostasis, 2012
- Propranolol en hemangiomas infantiles: eficacia clínica, riesgos y recomendacionesActas Dermo-Sifiliograficas, 2011
- Effects of genistein on early-stage cutaneous wound healingBiochemical and Biophysical Research Communications, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasiaLiver Transplantation, 2008
- Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and DiseaseEndocrine Reviews, 2007
- Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): Association with venous thromboembolismThrombosis and Haemostasis, 2007
- Therapeutic action of tranexamic acid in hereditary haemorrhagic telangiectasia (HHT): Regulation of ALK-1/endoglin pathway in endothelial cellsThrombosis and Haemostasis, 2007
- Biology of vascular endothelial growth factorsFEBS Letters, 2006