Fiege Lina, Duran Ibrahim, Marquardt Thorsten
Department of General Pediatrics, Metabolic Diseases, University Children's Hospital Münster, 48149 Münster, Germany.
Center of Prevention and Rehabilitation, UniReha, Medical Faculty and University Hospital of Cologne, 50931 Cologne, Germany.
Pharmaceuticals (Basel). 2023 Aug 23;16(9):1199. doi: 10.3390/ph16091199.
Pompe disease is a lysosomal storage disorder with impaired glycogen degradation caused by a deficiency of the enzyme acid α-glucosidase (GAA). Children with the severe infantile form do not survive beyond the first year of life without treatment. Since 2006, enzyme replacement therapy (ERT) with Alglucosidase alfa (Myozyme) has been available, which is a recombinant human GAA (rhGAA). Myozyme therapy has prolonged the life span of affected patients, but many patients showed a continuing, albeit slower, disease progression. A new generation of rhGAA, Cipaglucosidase alfa (Amicus) has a higher content of mannose-6-phosphate residues, which are necessary for efficient cellular uptake and lysosomal targeting. Cipaglucosidase alfa is co-administered with an enzyme stabilizer, Miglustat, which also optimizes the pharmacological properties. In mouse models, the superiority of Cipaglucosidase alfa/Miglustat compared to the previous standard therapy could be determined. Here, we report the disease course of a patient with severe infantile M. Pompe, who showed serious progression even with high-dose standard of care ERT. Changing the therapy to Cipaglucosidase alfa/Miglustat improved respiratory failure, cardiomyopathy, and motor functions significantly. The patient could be weaned from respiratory support and oxygen supplementation. Cardiac function was normalized. Most impressively, the patient, who had lost nearly all motor skills, acquired head control, learned to speak, and could move his wheelchair by himself. Overall, the patient's clinical situation has improved dramatically with the new ERT.
庞贝病是一种溶酶体贮积症，因缺乏酸性α-葡萄糖苷酶（GAA）导致糖原降解受损。严重婴儿型患者若不治疗，生存期不超过一岁。自2006年起，可用阿糖苷酶α（美而赞）进行酶替代疗法（ERT），它是一种重组人GAA（rhGAA）。美而赞疗法延长了受影响患者的寿命，但许多患者仍表现出疾病持续进展，尽管进展较慢。新一代rhGAA，cipaglucosidase alfa（阿密库斯）含有更高含量的6-磷酸甘露糖残基，这对有效的细胞摄取和溶酶体靶向至关重要。Cipaglucosidase alfa与一种酶稳定剂米格列醇联合使用，米格列醇也优化了其药理特性。在小鼠模型中，可以确定cipaglucosidase alfa/米格列醇相比先前标准疗法的优越性。在此，我们报告一名严重婴儿型庞贝病患者的病程，该患者即使接受高剂量标准护理ERT仍表现出严重进展。将治疗改为cipaglucosidase alfa/米格列醇后，呼吸衰竭、心肌病和运动功能得到显著改善。患者可以脱离呼吸支持和吸氧。心脏功能恢复正常。最令人印象深刻的是，几乎丧失所有运动技能的患者获得了头部控制能力，学会了说话，并能自己推动轮椅。总体而言，采用新的ERT后，患者的临床状况有了显著改善。
