Servais Laurent, Montus Marie, Guiner Caroline Le, Ben Yaou Rabah, Annoussamy Mélanie, Moraux Amélie, Hogrel Jean-Yves, Seferian Andreea M, Zehrouni Karima, Le Moing Anne-Gaëlle, Gidaro Teresa, Vanhulle Catherine, Laugel Vincent, Butoianu Nina, Cuisset Jean-Marie, Sabouraud Pascal, Cances Claude, Klein Andrea, Leturcq France, Moullier Philippe, Voit Thomas
Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
Généthon, Evry, France.
J Neuromuscul Dis. 2015 Sep 2;2(3):269-279. doi: 10.3233/JND-150100.
Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that induce skipping of exon 51, 44, 45, or 53 are currently being evaluated in clinical trials. These trials were designed on the basis of data available in general DMD population.
Our objective was to compare the clinical and functional statuses of non-ambulant DMD patients theoretically treatable by exon 53 skipping and of DMD patients with other mutations.
We first compared fifteen non-ambulant DMD patients carrying deletions theoretically treatable by exon 53 skipping (DMD-53) with fifteen closely age-matched DMD patients with mutations not treatable by exon 53 skipping (DMD-all-non-53) then with fifteen DMD patients carrying deletions not treatable by exon 53 skipping (DMD-del-non-53).
We found that DMD-53 patients had a lower left ventricular ejection fraction, more contractures and they tend to have weaker grips and pinch strengths than other DMD patients. DMD-53 patients lost ambulation significantly younger than other DMD patients. This result was confirmed by comparing ages at loss of ambulation in all non-ambulant DMD patients of the DMD cohort identified in a molecular diagnostic lab.
These prospective and retrospective data demonstrate that DMD-53 patients have clinically more severe phenotypes than other DMD patients.
外显子跳跃疗法是杜氏肌营养不良症（DMD）治疗中的一种新兴方法。目前，诱导外显子51、44、45或53跳跃的反义寡核苷酸正在临床试验中进行评估。这些试验是基于一般DMD人群的现有数据设计的。
我们的目的是比较理论上可通过外显子53跳跃治疗的非行走型DMD患者与其他突变类型DMD患者的临床和功能状态。
我们首先将15名携带理论上可通过外显子53跳跃治疗的缺失突变的非行走型DMD患者（DMD-53）与15名年龄匹配的、携带无法通过外显子53跳跃治疗的突变的DMD患者（DMD-全非53）进行比较，然后与15名携带无法通过外显子53跳跃治疗的缺失突变的DMD患者（DMD-缺失非53）进行比较。
我们发现，与其他DMD患者相比，DMD-53患者的左心室射血分数较低，挛缩更多，握力和捏力往往更弱。DMD-53患者失去行走能力的年龄明显比其他DMD患者小。通过比较分子诊断实验室确定的DMD队列中所有非行走型DMD患者失去行走能力的年龄，这一结果得到了证实。
这些前瞻性和回顾性数据表明，DMD-53患者的临床表型比其他DMD患者更严重。
