Hereditary Hemorrhagic Telangiectasia (HHT), also known as Rendu-Osler syndrome, is a genetic vascular disorder affecting 1 in 5000-8000 individuals worldwide. This rare disease is characterized by various vascular defects including epistaxis, blood vessel dilations (telangiectasia) and arteriovenous malformations (AVM) in several organs. About 90% of the cases are associated with heterozygous mutations of ACVRL1 or ENG genes, that respectively encode a bone morphogenetic protein receptor (activin receptor-like kinase 1, ALK1) and a co-receptor named endoglin. Less frequent mutations found in the remaining 10% of patients also affect the gene SMAD4 which is part of the transcriptional complex directly activated by this pathway. Presently, the therapeutic treatments for HHT are intended to reduce the symptoms of the disease. However, recent progress has been made using drugs that target VEGF (vascular endothelial growth factor) and the angiogenic pathway with the use of bevacizumab (anti-VEGF antibody). Furthermore, several exciting high-throughput screenings and preclinical studies have identified new molecular targets directly related to the signaling pathways affected in the disease. These include FKBP12, PI3-kinase and angiopoietin-2. This review aims at reporting these recent developments that should soon allow a better care of HHT patients.

中文翻译：

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遗传性出血性毛细血管扩张的未来治疗。

遗传性出血性毛细血管扩张症（HHT），也称为Rendu-Osler综合征，是一种遗传性血管疾病，影响全世界5000-8000个人中的1个人。这种罕见疾病的特征是多种血管缺陷，包括鼻出血，血管扩张（毛细血管扩张）和一些器官的动静脉畸形（AVM）。大约90％的病例与ACVRL1或ENG基因的杂合突变有关，它们分别编码一个骨形态发生蛋白受体（激活素受体样激酶1，ALK1）和一个称为内皮糖蛋白的共受体。在其余10％的患者中发现的频率较低的突变也会影响SMAD4基因，该基因是该途径直接激活的转录复合体的一部分。目前，HHT的治疗方法旨在减轻疾病的症状。然而，使用贝伐单抗（抗VEGF抗体）使用靶向VEGF（血管内皮生长因子）和血管生成途径的药物已取得了最新进展。此外，一些激动人心的高通量筛选和临床前研究已经确定了与疾病中受影响的信号通路直接相关的新分子靶标。这些包括FKBP12，PI3-激酶和血管生成素-2。这篇综述的目的是报告这些近期的进展，这些进展将很快使HHT患者得到更好的护理。几项令人兴奋的高通量筛选和临床前研究已经确定了与疾病中受影响的信号通路直接相关的新分子靶标。这些包括FKBP12，PI3-激酶和血管生成素-2。这篇综述的目的是报告这些近期的进展，这些进展将很快使HHT患者得到更好的护理。几项令人兴奋的高通量筛选和临床前研究已经确定了与疾病中受影响的信号通路直接相关的新分子靶标。这些包括FKBP12，PI3-激酶和血管生成素-2。这篇综述的目的是报告这些近期的进展，这些进展将很快使HHT患者得到更好的护理。