Abstract:
Wolfram syndrome (WS), also known as a DIDMOAD (diabetes insipidus, early-onset diabetes mellitus, optic nerve atrophy and deafness) is a rare autosomal disorder caused by mutations in the Wolframin1 (WFS1) gene. Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP1 RA) are effective in delaying and restoring blood glucose control in WS animal models and patients. The GLP1 RA liraglutide has also been shown to have neuroprotective properties in aged WS rats. WS is an early-onset, chronic condition. Therefore, early diagnosis and lifelong pharmacological treatment is the best solution to control disease progression. Hence, the aim of this study was to evaluate the efficacy of the long-term liraglutide treatment on the progression of WS symptoms. For this purpose, 2-month-old WS rats were treated with liraglutide up to the age of 18 months and changes in diabetes markers, visual acuity, and hearing sensitivity were monitored over the course of the treatment period. We found that treatment with liraglutide delayed the onset of diabetes and protected against vision loss in a rat model of WS. Therefore, early diagnosis and prophylactic treatment with the liraglutide may also prove to be a promising treatment option for WS patients by increasing the quality of life.
摘要:
Wolfram综合征(WS),也称为DIDMOAD(尿崩症,早发糖尿病,视神经萎缩和耳聋)是一种罕见的常染色体疾病,由Wolframin1(WFS1)基因突变引起。先前的研究表明,胰高血糖素样肽-1受体激动剂(GLP1RA)可有效延迟和恢复WS动物模型和患者的血糖控制。GLP1RA利拉鲁肽也已被证明在老年WS大鼠中具有神经保护特性。WS是早发,慢性疾病。因此,早期诊断和终身药物治疗是控制疾病进展的最佳解决方案。因此,本研究的目的是评估长期利拉鲁肽治疗对WS症状进展的疗效.为此,2月龄的WS大鼠用利拉鲁肽治疗至18月龄,糖尿病标志物的变化,视敏度,在治疗期间监测听力敏感度。我们发现,在WS大鼠模型中,用利拉鲁肽治疗可延迟糖尿病的发作并防止视力丧失。因此,利拉鲁肽的早期诊断和预防性治疗也可能被证明是WS患者有希望的治疗选择,它能提高患者的生活质量.