Long-Term Pulmonary Function in Duchenne Muscular Dystrophy: Comparison of Eteplirsen-Treated Patients to Natural History.

Autor:	Kinane TB; Division of Pediatric Pulmonary, Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA, USA., Mayer OH; Division of Pulmonology Pediatric Pulmonary, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Duda PW; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Lowes LP; Department of Neurology, Nationwide Children's Hospital, Columbus, OH, USA.; Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, Rochester, NY, USA., Moody SL; PharPoint Research, Durham, NC, USA., Mendell JR; Department of Neurology, Nationwide Children's Hospital, Columbus, OH, USA.; Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, Rochester, NY, USA.; Department of Pediatrics and Neurology, Ohio State University, Columbus, OH, USA.
Jazyk:	angličtina
Zdroj:	Journal of neuromuscular diseases [J Neuromuscul Dis] 2018; Vol. 5 (1), pp. 47-58.
DOI:	10.3233/JND-170272
Abstrakt:	Background: Duchenne muscular dystrophy (DMD) is a rare, degenerative, X-linked genetic disease that results in progressive muscle loss and premature death, most commonly from respiratory or cardiac failure. DMD is primarily caused by whole exon deletions, resulting in a shift of the dystrophin mRNA reading frame that prevents production of functional dystrophin protein. Eteplirsen, a phosphorodiamidate morpholino oligomer (PMO), is designed to skip exon 51, restore the reading frame, and induce production of internally shortened dystrophin in patients with mutations amenable to such treatment. Objective: Describe lung function assessed throughout eteplirsen studies 201/202. Methods: Studies 201/202 included 12 patients treated with eteplirsen over 5 years. Pulmonary function tests included forced vital capacity (FVC), maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP). With no long-term placebo control, FVC results were compared with data from the United Dystrophinopathy Project (UDP). MIP and MEP were compared to published natural history. Results: Age-adjusted mixed-model repeated-measures analysis showed decreases of 2.3% and 2.6% annually for FVC% p and MEP% p, and an annual increase of 0.6% for MIP% p for the eteplirsen-treated cohort. Data from the UDP demonstrated a 4.1% decline in FVC% p. The published natural history reports annual declines of at least 2.7% and 3.8% for MEP% p and MIP% p, respectively, in patients with DMD. Conclusions: With eteplirsen treatment, deterioration of respiratory muscle function based on FVC% p was half of that seen in the UDP; MEP% p and MIP% p compared favorably with natural history.
Databáze:	MEDLINE
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