Haddley K
Liverpool, UK.
Drugs Today (Barc). 2014 Jul;50(7):475-83. doi: 10.1358/dot.2014.50.7.2177904.
Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome, is an inherited, lysosomal storage disorder caused by genetic mutations in N-acetylgalactosamine-6-sulfatase (GALNS) enzyme gene. GALNS is essential for breakdown of glycosaminoglycans. The disease is characterized by the early onset of severe skeletal dysplasia resulting in significant disability by the second decade of life. Until recently there have been no available treatments other than surgery and palliative care. BioMarin Pharmaceutical developed elosulfase alfa, a recombinant human GALNS coproduced with sulfatase-modifying factor 1, as an enzyme replacement therapy for patients with MPS IVA. In clinical studies, enzyme replacement therapy with elosulfase alfa significantly improved physical endurance, respiratory function, growth and quality of life in patients with MPS IVA. Treatment increased clearance of glycosaminoglycans and induced gene expression consistent with improved chondrocyte function. Elosulfase alfa is approved for the treatment of MPS IVA in the U.S. and Europe.
IVA型黏多糖贮积症(MPS IVA),也称为莫尔基奥A综合征,是一种遗传性溶酶体贮积症,由N-乙酰半乳糖胺-6-硫酸酯酶(GALNS)基因的基因突变引起。GALNS对糖胺聚糖的分解至关重要。该疾病的特征是严重骨骼发育异常早发,在生命的第二个十年导致严重残疾。直到最近,除了手术和姑息治疗外,没有其他可用的治疗方法。BioMarin制药公司开发了阿加糖酶α,一种与硫酸酯酶修饰因子1共同产生的重组人GALNS,作为MPS IVA患者的酶替代疗法。在临床研究中,阿加糖酶α酶替代疗法显著改善了MPS IVA患者的身体耐力、呼吸功能、生长和生活质量。治疗增加了糖胺聚糖的清除率,并诱导了与软骨细胞功能改善一致的基因表达。阿加糖酶α在美国和欧洲被批准用于治疗MPS IVA。