The US Food and Drug Administration has approved the first therapy for metachromatic leukodystrophy (MLD), a rare fatal genetic disorder. The lysosomal storage disease affects about 40 children each year in the USA. It is caused by a mutation in the gene encoding the arylsulfatase enzyme that leads to progressive demyelination and progressive loss of motor and cognitive functions. There were previously no treatments. The new gene therapy, Orchard Therapeutics’ Lenmeldy (atidarsagene autotemcel), has a price tag of $4.25 million, making it the world’s most expensive drug. It inserts functional copies of the arylsulfatase A (ARSA) gene into the patient’s own hematopoietic stem ex vivo with a lentiviral vector. The repaired stem cells are re-infused, correcting the enzyme deficiency and preventing the harmful buildup of sulfatide fats that cause nerve cell demyelination.

The approval is based on results from 37 pediatric patients showing that Lenmeldy improved motor impairment and survival compared with the natural history of MLD. All presymptomatic patients treated with Lenmeldy who had the late infantile form of MLD were alive at age 6 years, compared with just over half of the natural history group. Treated patients could walk and had normal language and cognitive skills. In patients with pre- or early symptomatic juvenile forms of MLD, the gene therapy also slowed motor and cognitive decline.

美国食品和药物管理局已批准首个治疗异染性脑白质营养不良（MLD）的疗法，这是一种罕见的致命遗传性疾病。在美国，溶酶体贮积症每年影响约 40 名儿童。它是由编码芳基硫酸酯酶的基因突变引起的，导致进行性脱髓鞘以及运动和认知功能的进行性丧失。之前没有任何治疗方法。 Orchard Therapeutics 的 Lenmeldy (atidarsagene autotemcel) 这种新型基因疗法的标价为 425 万美元，使其成为世界上最昂贵的药物。它将芳基硫酸酯酶 A ( ARSA ) 基因的功能性拷贝通过慢病毒载体离体插入患者自身的造血干中。修复后的干细胞被重新注入，纠正酶缺陷并防止导致神经细胞脱髓鞘的硫苷脂有害积聚。

此次批准基于 37 名儿科患者的结果，该结果显示，与 MLD 自然史相比，Lenmeldy 改善了运动障碍和生存率。所有接受 Lenmeldy 治疗的患有晚期婴儿型 MLD 的症状前患者在 6 岁时均存活，而自然病史组的这一比例略高于一半。接受治疗的患者可以行走并具有正常的语言和认知能力。对于患有早期或早期症状性青少年型 MLD 的患者，基因治疗还减缓了运动和认知能力的下降。