Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan inherited lysosomal storage disease and one of the most common MPS subtypes. The classical presentation is an infantile‐onset neurodegenerative disease characterised by intellectual regression, behavioural and sleep disturbances, loss of ambulation, and early death. Unlike other MPS, no disease‐modifying therapy has yet been approved. Here, we review the numerous approaches of curative therapy developed for MPS III from historical ineffective haematopoietic stem cell transplantation and substrate reduction therapy to the promising ongoing clinical trials based on enzyme replacement therapy or adeno‐associated or lentiviral vectors mediated gene therapy. Preclinical studies are presented alongside the most recent translational first‐in‐man trials. In addition, we present experimental research with preclinical mRNA and gene editing strategies. Lessons from animal studies and clinical trials have highlighted the importance of an early therapy before extensive neuronal loss. A disease‐modifying therapy for MPS III will undoubtedly mandate development of new strategies for early diagnosis.

中文翻译：

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III 型粘多糖贮积症的新疗法


III 型粘多糖贮积症 (MPS III) 或 Sanfilippo 病是一种孤儿遗传性溶酶体贮积病，也是最常见的 MPS 亚型之一。典型的表现是一种婴儿期发病的神经退行性疾病，其特征是智力退化、行为和睡眠障碍、行走能力丧失和过早死亡。与其他 MPS 不同，尚未批准任何疾病缓解疗法。在此，我们回顾了针对 MPS III 开发的多种治疗方法，从历史上无效的造血干细胞移植和底物减少疗法，到正在进行的基于酶替代疗法或腺相关或慢病毒载体介导的基因治疗的有希望的临床试验。临床前研究与最新的转化性首次人体试验一起呈现。此外，我们还提供临床前 mRNA 和基因编辑策略的实验研究。动物研究和临床试验的经验教训强调了在神经元广泛损失之前进行早期治疗的重要性。 MPS III 的疾病修饰疗法无疑需要制定新的早期诊断策略。