Guémy C, Laforêt P
Neurology Department, Nord-Est-Île-de-France Neuromuscular Reference Center, Raymond-Poincaré Hospital, AP-HP, Garches, France.
Neurology Department, Nord-Est-Île-de-France Neuromuscular Reference Center, Raymond-Poincaré Hospital, AP-HP, Garches, France; FHU PHENIX, Garches, France.
Rev Neurol (Paris). 2023 Jan-Feb;179(1-2):81-89. doi: 10.1016/j.neurol.2022.12.004. Epub 2023 Jan 4.
Late-onset Pompe disease (LOPD) is a genetic myopathy causing skeletal muscle weakness and severe respiratory impairment, due to the deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) leading to lysosomal glycogen accumulation along with other complex pathophysiological processes. A major step for treatment of Pompe disease was reached in 2006 with the marketing of alglucosidase alfa, a first enzyme replacement therapy (ERT) that showed a significant motor and respiratory benefit. However, efficacy of alglucosidase alfa is limited in LOPD with a loss of efficacy over time, promoting research on new treatments. Next-generation ERT are new enzymes biochemically modified to increase the uptake of exogenous enzyme by target tissues, and the benefit of two recombinant enzymes (avalglucosidase alfa and cipaglucosidase alfa) has been recently studied in large phase III clinical trials, the latest combined with miglustat. Several innovative therapies, based on GAA gene transfer, antisense oligonucleotides or inhibition of glycogen synthesis with substrate reduction therapy, are currently under study, but are still at an early stage of development. Overall, active research for new treatments raises hope for LOPD patients but challenges remain for the clinician with the need for reliable efficacy assessment tools, long-term registry data, and evidence-based recommendations for the best use of these new molecules recently available or under development.
晚发型庞贝病（LOPD）是一种遗传性肌病，可导致骨骼肌无力和严重的呼吸功能障碍，这是由于溶酶体酶酸性α-葡萄糖苷酶（GAA）缺乏，导致溶酶体糖原积累以及其他复杂的病理生理过程。2006年，随着第一种酶替代疗法（ERT）阿糖苷酶α上市，庞贝病治疗取得了重大进展，该疗法显示出显著的运动和呼吸益处。然而，阿糖苷酶α在LOPD中的疗效有限，且随着时间推移疗效会丧失，这推动了对新治疗方法的研究。新一代ERT是经过生物化学修饰的新酶，以增加靶组织对外源酶的摄取，最近在大型III期临床试验中研究了两种重组酶（阿伐糖苷酶α和西帕糖苷酶α）的益处，最新研究将西帕糖苷酶α与米格列醇联合使用。目前正在研究几种基于GAA基因转移、反义寡核苷酸或用底物减少疗法抑制糖原合成的创新疗法，但仍处于早期开发阶段。总体而言，对新治疗方法的积极研究给LOPD患者带来了希望，但临床医生仍面临挑战，需要可靠的疗效评估工具、长期登记数据以及关于最佳使用这些最近可用或正在开发的新分子的循证建议。
