Twelve caregivers were recruited, reporting on 12 children with MLD. Children had a mean age of 6.1 years; mean age at symptom onset was 17.6 months. Most children (10/12) progressed from walking without support (categories 0-1) to a loss of locomotion (categories 5-6) in ≤ 2 years. Caregivers felt that GMFC-MLD and ELFC-MLD accurately described motor and language declines in their children, respectively. Most caregivers (10/12) reported that the idea of delaying disease progression would be meaningful. Further, a slowing of motor function decline in GMFC-MLD, from category 1 to category 3 or from category 2 to category 4 over 2 years, was seen as meaningful by all caregivers asked; however, only 3/12 caregivers reported that delayed decline would be meaningful if baseline category was ≥ 3. Caregivers also reported that delaying expressive language decline at any level that did not indicate a complete loss of expressive language (indicated by categories 1-3) would be meaningful.
Caregivers of children with MLD felt that a delayed decline in gross motor function, as assessed by the GMFC-MLD, would be meaningful, supporting the selection of primary and secondary endpoints for the phase 2 clinical trial. Communication abilities were another area of significance for consideration in future clinical trial design.
结果:招募了12名护理人员,报告了12名患有MLD的儿童。儿童的平均年龄为6.1岁;症状发作的平均年龄为17.6个月。大多数儿童(10/12)在≤2年内从无支撑行走(0-1类)发展到失去运动能力(5-6类)。看护者认为GMFC-MLD和ELFC-MLD准确地描述了孩子的运动和语言下降,分别。大多数护理人员(10/12)报告说,延迟疾病进展的想法是有意义的。Further,GMFC-MLD运动功能下降的减慢,在2年内从类别1到类别3或从类别2到类别4,被所有被问到的护理人员认为是有意义的;然而,只有3/12的护理人员报告,如果基线类别≥3,则延迟下降是有意义的.看护者还报告说,在任何水平上延迟表达性语言下降,而这并不表明表达性语言的完全丧失(由类别1-3表示)都是有意义的。
结论:患有MLD的儿童的照顾者认为运动粗大功能的延迟下降,根据GMFC-MLD的评估,会有意义,支持选择2期临床试验的主要和次要终点.沟通能力是未来临床试验设计中需要考虑的另一个重要领域。