Sanchez Phillip, Farkhondeh Atena, Pavlinov Ivan, Baumgaertel Karsten, Rodems Steven, Zheng Wei
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, United States.
Travere Therapeutics, San Diego, CA, United States.
Front Pharmacol. 2021 Aug 23;12:704586. doi: 10.3389/fphar.2021.704586. eCollection 2021.
Advancements in treatment for the rare genetic disorder known as Alagille Syndrome (ALGS) have been regrettably slow. The large variety of mutations to the JAG1 and NOTCH2 genes which lead to ALGS pose a unique challenge for developing targeted treatments. Due to the central role of the Notch signaling pathway in several cancers, traditional treatment modalities which compensate for the loss in activity caused by mutation are rightly excluded. Unfortunately, current treatment plans for ALGS focus on relieving symptoms of the disorder and do not address the underlying causes of disease. Here we review several of the current and potential key technologies and strategies which may yield a significant leap in developing targeted therapies for this disorder.
令人遗憾的是，针对罕见遗传病阿拉吉耶综合征（ALGS）的治疗进展一直缓慢。导致ALGS的JAG1和NOTCH2基因存在大量突变，这给开发靶向治疗带来了独特挑战。由于Notch信号通路在多种癌症中发挥核心作用，因此补偿由突变导致的活性丧失的传统治疗方式被合理排除。不幸的是，目前ALGS的治疗方案侧重于缓解该疾病的症状，而未解决疾病的根本原因。在此，我们综述了几种当前和潜在的关键技术与策略，这些技术与策略可能会在开发针对该疾病的靶向疗法方面取得重大飞跃。
