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Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis.
Molecular Genetics and Metabolism Reports ( IF 1.9 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.ymgmr.2020.100586
Dawn Phillips 1 , Julia B Hennermann 2 , Anna Tylki-Szymanska 3 , Line Borgwardt 4, 5 , Mercedes Gil-Campos 6 , Nathalie Guffon 7 , Yasmina Amraoui 8 , Silvia Geraci 9 , Diego Ardigò 9 , Federica Cattaneo 9 , Allan M Lund 4
Affiliation  

Objectives

Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder resulting from deficient lysosomal alpha-mannosidase activity. Clinical manifestations include progressive balance disorders, immune deficiency, skeletal abnormalities and cognitive deficits beginning in early childhood. Enzyme replacement therapy with recombinant human alpha-mannosidase (velmanase alfa) is scheduled for clinical development in the US beginning in 2020 and has been approved in the EU for treatment of non-neurological manifestations in cases of mild to moderate disease. This study assessed effects of velmanase alfa on fine and gross motor proficiency in children and adults.

Methods

Integrated Bruininks-Oseretsky (BOT-2) test of Motor Proficiency data from velmanase alfa clinical trials was stratified by age for 14 adults and 19 children treated for up to 4 years.

Results

Patients showed global developmental delays at baseline. For the combined adult and pediatric group there was a statistically significant increase (improvement) in BOT-2 total point score of 13% (p = .035, 95% CI 1.0, 25.0) from baseline to last observation. When stratified by pediatric versus adult patients, there was improvement in BOT-2 total point score in patients <18 years (mean percent increase from baseline to last observation 23%) compared to adults (mean decrease of −0.7%). Subtest analysis of individual BOT-2 items captured some improvement following velmanase alfa treatment in pediatric patients.

Conclusions

There was limited ability to assess the BOT-2 change responses in adults. Pediatric patients showed stability or improvement in scaled scores relative to healthy peers, indicating continued skill acquisition, which may increase independence and contribute to improved patient quality of life.



中文翻译:

使用 Bruininks-Oseretsky 运动能力测试 (BOT-2) 评估 velmanase alfa 作为 α-甘露糖苷沉着症的酶疗法的疗效。

目标

α-甘露糖苷病是一种罕见的常染色体隐性遗传溶酶体贮积症,由溶酶体α-甘露糖苷酶活性不足引起。临床表现包括从儿童早期开始的进行性平衡障碍、免疫缺陷、骨骼异常和认知缺陷。重组人α-甘露糖苷酶 (velmanase alfa) 的酶替代疗法计划于 2020 年开始在美国进行临床开发,并已在欧盟获得批准,用于治疗轻度至中度疾病的非神经系统表现。本研究评估了维曼酶 alfa 对儿童和成人精细和粗大运动能力的影响。

方法

来自 velmanase alfa 临床试验的运动能力数据的综合 Bruininks-Oseretsky (BOT-2) 测试按年龄对 14 名成人和 19 名接受治疗长达 4 年的儿童进行分层。

结果

患者在基线时表现出整体发育迟缓。对于成人和儿童联合组,从基线到最后一次观察,BOT-2 总分有 13% 的统计显着增加(改善)(p = .035, 95% CI 1.0, 25.0)。当按儿童与成人患者分层时,与成人(平均下降 -0.7%)相比,<18 岁患者的 BOT-2 总分有所改善(从基线到最后一次观察的平均百分比增加 23%)。对个别 BOT-2 项目的子测试分析在儿科患者的 velmanase alfa 治疗后发现了一些改善。

结论

评估成人 BOT-2 变化反应的能力有限。与健康同龄人相比,儿科患者的量表分数表现出稳定或改善,表明持续获得技能,这可能会增加独立性并有助于改善患者的生活质量。

更新日期:2020-04-08
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