Panfili Eleonora, Frontino Giulio, Pallotta Maria Teresa
Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Hospital, Milano, Italy.
Front Clin Diabetes Healthc. 2023 Jun 2;4:1171091. doi: 10.3389/fcdhc.2023.1171091. eCollection 2023.
WFS1 spectrum disorder (WFS1-SD) is a rare monogenic neurodegenerative disorder whose cardinal symptoms are childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological signs ranging from mild to severe. The prognosis is poor as most patients die prematurely with severe neurological disabilities such as bulbar dysfunction and organic brain syndrome. Mutation of the gene is recognized as the prime mover of the disease and responsible for a dysregulated ER stress signaling, which leads to neuron and pancreatic β-cell death. There is no currently cure and no treatment that definitively arrests the progression of the disease. GLP-1 receptor agonists appear to be an efficient way to reduce elevated ER stress and , and increasing findings suggest they could be effective in delaying the progression of WFS1-SD. Here, we summarize the characteristics of GLP-1 receptor agonists and preclinical and clinical data obtained by testing them in WFS1-SD as a feasible strategy for managing this disease.
WFS1 谱系障碍（WFS1-SD）是一种罕见的单基因神经退行性疾病，其主要症状为儿童期发病的糖尿病、视神经萎缩、耳聋、尿崩症以及程度不一的神经学体征，从轻度到重度皆有。预后较差，因为大多数患者会过早死亡，并伴有严重的神经功能障碍，如延髓功能障碍和器质性脑综合征。该基因的突变被认为是疾病的主要推动者，并且导致内质网应激信号失调，进而导致神经元和胰腺β细胞死亡。目前尚无治愈方法，也没有能明确阻止疾病进展的治疗手段。胰高血糖素样肽-1（GLP-1）受体激动剂似乎是降低内质网应激升高及[此处原文缺失部分内容]的有效方法，越来越多的研究结果表明它们可能有效延缓WFS1-SD的进展。在此，我们总结GLP-1受体激动剂的特性以及通过在WFS1-SD中进行测试所获得的临床前和临床数据，将其作为管理该疾病的一种可行策略。
