PDF(Pubmed)
Abstract：
Gaucher disease (GD) is mainly caused by glucocerebrosidase (GCase) enzyme deficiency due to genetic variations in the GBA1 gene leading to the toxic accumulation of sphingolipids in various organs, which causes symptoms such as anemia, thrombocytopenia, hepatosplenomegaly, and neurological manifestations. GD is clinically classified into the non-neuronopathic type 1, and the acute and chronic neuronopathic forms, types 2 and 3, respectively. In addition to the current approved GD medications, the repurposing of Ambroxol (ABX) has emerged as a prospective enzyme enhancement therapy option showing its potential to enhance mutated GCase activity and reduce glucosylceramide accumulation in GD-affected tissues of different GBA1 genotypes. The variability in response to ABX varies across different variants, highlighting the diversity in patients\' therapeutic outcomes. Its oral availability and safety profile make it an attractive option, particularly for patients with neurological manifestations. Clinical trials are essential to explore further ABX\'s potential as a therapeutic medication for GD to encourage pharmaceutical companies\' investment in its development. This review highlights the potential of ABX as a pharmacological chaperone therapy for GD and stresses the importance of addressing response variability in clinical studies to improve the management of this rare and complex disorder.
摘要：
戈谢病（GD）主要是由葡萄糖脑苷脂酶（GCase）酶缺乏引起的，由于GBA1基因的遗传变异导致鞘脂在各个器官中的毒性积累，导致贫血等症状，血小板减少症,肝脾肿大,和神经表现。GD在临床上分为非神经病态1型，急性和慢性神经病态，类型2和3，分别。除了目前批准的GD药物，氨溴索(ABX)的再利用已成为一种前瞻性酶增强治疗选择,显示出其在不同GBA1基因型的GD感染组织中增强突变GCase活性和减少葡萄糖神经酰胺积累的潜力.响应ABX的变异性在不同的变体中变化，突出患者治疗结果的多样性。它的口服可用性和安全性使其成为一个有吸引力的选择，特别是对于有神经系统表现的患者。临床试验对于进一步探索ABX作为GD治疗药物的潜力，以鼓励制药公司对其开发进行投资至关重要。这篇综述强调了ABX作为GD的药物伴侣疗法的潜力，并强调了在临床研究中解决反应变异性以改善这种罕见和复杂疾病的管理的重要性。
