Istaiti Majdolen, Yahalom Gilad, Cohen Mikhal, Skrahina Volha, Skrahin Aliaksandr, Lukas Jan, Rolfs Arndt, Zimran Ari
Agyany Pharma Ltd., Jerusalem 9695614, Israel.
Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
Int J Mol Sci. 2025 Apr 6;26(7):3435. doi: 10.3390/ijms26073435.
Sidransky syndrome represents a distinct variant of Parkinson's disease (PD) that is linked to pathogenic variants in the glucocerebrosidase () gene. This disorder exhibits an earlier onset, a more severe course, and a higher dementia prevalence compared to idiopathic PD. While the pathogenesis remains debated between loss-of-function and gain-of-function mechanisms, targeted therapies are emerging. Pharmacological chaperones (PCs), like high-dose Ambroxol, aim to mitigate enzyme misfolding-a primary driver of this disorder-rather than addressing metabolic deficiencies seen in Gaucher disease. Despite failed trials of substrate reduction therapies, current clinical trials with Ambroxol and other PCs highlight promising avenues for disease modification. This commentary advocates for increased awareness of Sidransky syndrome to advance diagnostic strategies, promote genetic testing, and refine targeted treatments, with the potential to transform care for -related PD and prodromal stages of the disease.
西德兰斯基综合征是帕金森病（PD）的一种独特变体，与葡萄糖脑苷脂酶（）基因的致病变异有关。与特发性帕金森病相比，这种疾病起病更早，病程更严重，痴呆患病率更高。虽然发病机制在功能丧失和功能获得机制之间仍存在争议，但靶向治疗正在出现。像高剂量氨溴索这样的药理学伴侣（PCs）旨在减轻酶错误折叠——这种疾病的主要驱动因素——而不是解决戈谢病中出现的代谢缺陷。尽管底物减少疗法的试验失败了，但目前使用氨溴索和其他药理学伴侣的临床试验突出了疾病修饰的有前景的途径。这篇评论主张提高对西德兰斯基综合征的认识，以推进诊断策略，促进基因检测，并完善靶向治疗，有可能改变对相关帕金森病及其前驱阶段的治疗。
