Non-Ambulant Duchenne Patients Theoretically Treatable by Exon 53 Skipping have Severe Phenotype.
- Servais L Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Montus M Généthon, Evry, France.
- Guiner CL Généthon, Evry, France.
- Ben Yaou R Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Annoussamy M Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Moraux A Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Hogrel JY Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Seferian AM Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Zehrouni K Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Le Moing AG Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Gidaro T Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Vanhulle C Service de Pédiatrie, Centre Hospitalier Universitaire (CHU), Rouen, France.
- Laugel V Service de Pédiatrie, Centre Hospitalier Universitaire (CHU), Strasbourg, France.
- Butoianu N Pediatric Neurology Clinic, Alexandru Obregia Hospital, Bucharest, Romania.
- Cuisset JM Service de Neuropédiatrie, Centre hospitalier régional universitaire et faculté de médecine, Lille, France.
- Sabouraud P Service de Pédiatrie A, Hôpital Américain, CHU de Reims, Reims, France.
- Cances C Service de Neurologie Pédiatrique, Hôpital des Enfants, Toulouse, France.
- Klein A Department of pediatric neurology, University Children's Hospital, Zurich, Switzerland.
- Leturcq F Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- Moullier P Généthon, Evry, France.
- Voit T Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
- 2016-11-19
Published in:
- Journal of neuromuscular diseases. - 2015
English
BACKGROUND
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.
OBJECTIVES
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.
METHODS
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).
RESULTS
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.
CONCLUSIONS
These prospective and retrospective data demonstrate that DMD-53 patients have clinically more severe phenotypes than other DMD patients.
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.
OBJECTIVES
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.
METHODS
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).
RESULTS
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.
CONCLUSIONS
These prospective and retrospective data demonstrate that DMD-53 patients have clinically more severe phenotypes than other DMD patients.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.3233/JND-150100
- PMID 27858743
- Persistent URL
- https://sonar.rero.ch/global/documents/260494
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