Stevens David, Milani-Nejad Shadi, Mozaffar Tahseen
Departments of Neurology, 200 S. Manchester Avenue, Ste. 206, Orange, CA 92868, USA.
Pathology & Laboratory Medicine, School of Medicine, University of California, Irvine, USA.
Curr Treat Options Neurol. 2022 Nov;24(11):573-588. doi: 10.1007/s11940-022-00736-1. Epub 2022 Aug 4.
This review summarizes the clinical presentation and provides an update on the current strategies for diagnosis of Pompe disease. We will review the available treatment options. We examine newly approved treatments as well as upcoming therapies in this condition. We also provide commentary on the unmet needs in clinical management and research for this disease.
In March 2015, Pompe disease was added to the Recommended Uniform Screening Panel (RUSP) and since then a number of states have added Pompe disease to their slate of diseases for their Newborn Screening (NBS) program. Data emerging from these programs is revising our knowledge of incidence of Pompe disease. In 2021, two randomized controlled trials involving new forms of enzyme replacement therapy (ERT) were completed and one new product is already FDA-approved and on the market, whereas the other product will come up for FDA review in the fall. Neither of the new ERT were shown to be superior to the standard of care product, . The long-term effectiveness of these newer forms of ERT is unclear. Newer versions of the ERT are in development in addition to multiple different strategies of gene therapy to deliver GAA, the gene responsible for producing acid alpha-glucosidase, the defective protein in Pompe Disease. Glycogen substrate reduction is also in development in Pompe disease and other glycogen storage disorders.
There are significant unmet needs as it relates to clinical care and therapeutics in Pompe disease as well as in research. The currently available treatments lose effectiveness over the long run and do not have penetration into neuronal tissues and inconsistent penetration in certain muscles. More definitive gene therapy and enzyme replacement strategies are currently in development and testing.
本综述总结了庞贝病的临床表现，并提供了当前庞贝病诊断策略的最新信息。我们将回顾现有的治疗选择。我们研究了新批准的治疗方法以及针对这种疾病即将出现的疗法。我们还对这种疾病临床管理和研究中未满足的需求进行了评论。
2015年3月，庞贝病被添加到推荐统一筛查小组（RUSP）中，从那时起，许多州已将庞贝病添加到其新生儿筛查（NBS）计划的疾病清单中。这些计划中出现的数据正在修正我们对庞贝病发病率的认识。2021年，两项涉及新型酶替代疗法（ERT）的随机对照试验完成，一种新产品已获美国食品药品监督管理局（FDA）批准并上市，而另一种产品将于秋季接受FDA审查。新的ERT均未显示优于标准护理产品。这些新型ERT的长期有效性尚不清楚。除了多种不同的基因治疗策略来递送GAA（负责产生酸性α-葡萄糖苷酶的基因，这是庞贝病中缺陷蛋白）外，新型ERT也在研发中。糖原底物减少疗法也正在针对庞贝病和其他糖原贮积症进行研发。
在庞贝病的临床护理、治疗以及研究方面，仍存在重大未满足需求。目前可用的治疗方法从长远来看会失去效力，无法渗透到神经组织，在某些肌肉中的渗透也不一致。目前更明确的基因治疗和酶替代策略正在研发和测试中。
