Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Metabolic Rare Disease Unit, Pediatric Department, Fondazione MBBM, University of Milano Bicocca, Monza, Italy.
Ital J Pediatr. 2018 Nov 16;44(Suppl 2):124. doi: 10.1186/s13052-018-0564-z.
Enzyme replacement therapy is currently considered the standard of care for the treatment of mucopolysaccharidoses (MPS) type I, II, VI, and IV. This approach has shown substantial efficacy mainly on somatic symptoms of the patients, but no benefit was found for other clinical manifestations, such as neurological involvement. New strategies are currently being tested to address these limitations, in particular to obtain sufficient therapeutic levels in the brain. Intrathecal delivery of recombinant enzymes or chimeric enzymes represent promising approaches in this respect. Further innovation will likely be introduced by the recent advancements in the knowledge of lysosomal biology and function. It is now clear that the clinical manifestations of MPS are not only the direct effects of storage, but also derive from a cascade of secondary events that lead to dysfunction of several cellular processes and pathways. Some of these pathways may represent novel therapeutic targets and allow for development of novel or adjunctive therapies for these disorders.
酶替代疗法目前被认为是治疗黏多糖贮积症（MPS）I、II、VI 和 IV 的标准治疗方法。这种方法主要在患者的躯体症状方面显示出显著的疗效，但对其他临床表现，如神经受累，没有发现益处。目前正在测试新的策略来解决这些局限性，特别是在大脑中获得足够的治疗水平。鞘内给予重组酶或嵌合酶是这方面很有前途的方法。最近对溶酶体生物学和功能的认识的进展可能会带来进一步的创新。现在很清楚，MPS 的临床表现不仅是储存的直接影响，而且还源于一系列继发性事件，导致几种细胞过程和途径的功能障碍。其中一些途径可能代表新的治疗靶点，并为这些疾病开发新的或辅助治疗方法。
