Department of Pediatrics.
Department of Biochemistry & Molecular Biology, College of Medicine.
Curr Opin Neurol. 2023 Oct 1;36(5):464-473. doi: 10.1097/WCO.0000000000001187. Epub 2023 Jul 19.
Pompe disease is a rare, inherited, devastating condition that causes progressive weakness, cardiomyopathy and neuromotor disease due to the accumulation of glycogen in striated and smooth muscle, as well as neurons. While enzyme replacement therapy has dramatically changed the outcome of patients with the disease, this strategy has several limitations. Gene therapy in Pompe disease constitutes an attractive approach due to the multisystem aspects of the disease and need to address the central nervous system manifestations. This review highlights the recent work in this field, including methods, progress, shortcomings, and future directions.
Recombinant adeno-associated virus (rAAV) and lentiviral vectors (LV) are well studied platforms for gene therapy in Pompe disease. These products can be further adapted for safe and efficient administration with concomitant immunosuppression, with the modification of specific receptors or codon optimization. rAAV has been studied in multiple clinical trials demonstrating safety and tolerability.
Gene therapy for the treatment of patients with Pompe disease is feasible and offers an opportunity to fully correct the principal pathology leading to cellular glycogen accumulation. Further work is needed to overcome the limitations related to vector production, immunologic reactions and redosing.
庞贝病是一种罕见的遗传性进行性疾病，由于糖原在横纹肌和平滑肌以及神经元中的积累，导致进行性无力、心肌病和神经肌肉疾病。尽管酶替代疗法显著改变了患者的预后，但该策略存在一些局限性。由于疾病的多系统特征以及需要解决中枢神经系统表现，基因治疗构成了一种有吸引力的方法。本综述重点介绍了该领域的最新工作，包括方法、进展、缺点和未来方向。
重组腺相关病毒（rAAV）和慢病毒载体（LV）是庞贝病基因治疗的研究热点。这些产品可以通过同时进行免疫抑制，改变特定受体或密码子优化，进一步适用于安全有效的给药。rAAV 已在多项临床试验中进行了研究，证明了其安全性和耐受性。
基因治疗治疗庞贝病患者是可行的，并为纠正导致细胞糖原积累的主要病理提供了机会。需要进一步努力克服与载体生产、免疫反应和再给药相关的限制。
