Pane Marika, Mazzone Elena S, Sormani Maria Pia, Messina Sonia, Vita Gian Luca, Fanelli Lavinia, Berardinelli Angela, Torrente Yvan, D'Amico Adele, Lanzillotta Valentina, Viggiano Emanuela, D'Ambrosio Paola, Cavallaro Filippo, Frosini Silvia, Bello Luca, Bonfiglio Serena, Scalise Roberta, De Sanctis Roberto, Rolle Enrica, Bianco Flaviana, Van der Haawue Marlene, Magri Francesca, Palermo Concetta, Rossi Francesca, Donati Maria Alice, Alfonsi Chiara, Sacchini Michele, Arnoldi Maria Teresa, Baranello Giovanni, Mongini Tiziana, Pini Antonella, Battini Roberta, Pegoraro Elena, Previtali Stefano C, Napolitano Sara, Bruno Claudio, Politano Luisa, Comi Giacomo P, Bertini Enrico, Morandi Lucia, Gualandi Francesca, Ferlini Alessandra, Goemans Nathalie, Mercuri Eugenio
Department of Paediatric Neurology, Catholic University, Rome, Italy.
Biostatistics Unit, Department of Health Sciences, University of Genoa, Italy.
PLoS One. 2014 Jan 8;9(1):e83400. doi: 10.1371/journal.pone.0083400. eCollection 2014.
In the last few years some of the therapeutical approaches for Duchenne muscular dystrophy (DMD) are specifically targeting distinct groups of mutations, such as deletions eligible for skipping of individual exons. The aim of this observational study was to establish whether patients with distinct groups of mutations have different profiles of changes on the 6 minute walk test (6MWT) over a 12 month period.
The 6MWT was performed in 191 ambulant DMD boys at baseline and 12 months later. The results were analysed using a test for heterogeneity in order to establish possible differences among different types of mutations (deletions, duplications, point mutations) and among subgroups of deletions eligible to skip individual exons.
At baseline the 6MWD ranged between 180 and 560,80 metres (mean 378,06, SD 74,13). The 12 month changes ranged between -325 and 175 (mean -10.8 meters, SD 69.2). Although boys with duplications had better results than those with the other types of mutations, the difference was not significant. Similarly, boys eligible for skipping of the exon 44 had better baseline results and less drastic changes than those eligible for skipping exon 45 or 53, but the difference was not significant.
even if there are some differences among subgroups, the mean 12 month changes in each subgroup were all within a narrow Range: from the mean of the whole DMD cohort. This information will be of help at the time of designing clinical trials with small numbers of eligible patients.
在过去几年中,杜氏肌营养不良症(DMD)的一些治疗方法专门针对不同组别的突变,例如适合单个外显子跳跃的缺失。这项观察性研究的目的是确定具有不同突变组的患者在12个月期间的6分钟步行试验(6MWT)变化情况是否不同。
对191名能够行走的DMD男孩在基线时和12个月后进行了6MWT测试。使用异质性检验分析结果,以确定不同类型突变(缺失、重复、点突变)之间以及适合单个外显子跳跃的缺失亚组之间是否存在可能的差异。
基线时,6MWD在180至560.80米之间(平均378.06,标准差74.13)。12个月的变化在-325至175之间(平均-10.8米,标准差69.2)。虽然重复突变的男孩比其他类型突变的男孩结果更好,但差异不显著。同样,适合跳跃外显子44的男孩基线结果更好,变化也比适合跳跃外显子45或53的男孩小,但差异不显著。
即使各亚组之间存在一些差异,但每个亚组12个月的平均变化都在一个狭窄范围内:与整个DMD队列的平均值相比。这些信息在设计针对少数符合条件患者的临床试验时将有所帮助。