Brigham and Women's Hospital, Boston, MA, USA.
BioDrugs. 2024 Nov;38(6):743-753. doi: 10.1007/s40259-024-00680-3. Epub 2024 Sep 18.
Pulmonary arterial hypertension (PAH) is a rare and progressive disease that continues to remain highly morbid despite multiple advances in medical therapies. There remains a persistent and desperate need to identify novel methods of treating and, ideally, reversing the pathologic vasculopathy that results in PAH development and progression. Sotatercept is a first-in-class fusion protein that is believed to primarily inhibit activin signaling resulting in decreased cell proliferation and differentiation, though the exact mechanism remains uncertain. Here, we review the currently available PAH therapies, data highlighting the importance of transforming growth factor-β (TGF-β) superfamily signaling in the development of PAH, and the published and on-going clinical trials evaluating sotatercept in the treatment of PAH. We will also discuss preclinical data supporting the potential use of the fusion protein KER-012 in the inhibition of aberrant TGF-β superfamily signaling to ameliorate the obstructive vasculopathy of PAH.
肺动脉高压（PAH）是一种罕见且进行性的疾病，尽管在医学治疗方面取得了多项进展，但仍然高度致命。人们仍然迫切需要寻找新的治疗方法，理想情况下，逆转导致 PAH 发展和进展的病理性血管病变。Sotatercept 是一种首创的融合蛋白，据信主要抑制激活素信号，从而减少细胞增殖和分化，尽管确切机制仍不确定。在这里，我们回顾了目前可用的 PAH 治疗方法，强调转化生长因子-β（TGF-β）超家族信号在 PAH 发展中的重要性，以及正在进行的评估 sotatercept 治疗 PAH 的临床试验。我们还将讨论支持融合蛋白 KER-012 用于抑制异常 TGF-β 超家族信号以改善 PAH 的阻塞性血管病变的临床前数据。
