Omigapil Treatment Decreases Fibrosis and Improves Respiratory Rate in dy2J Mouse Model of Congenital Muscular Dystrophy

Introduction:Congenital muscular dystrophy is a distinct group of diseases presenting with weakness in infancy or childhood and no current therapy. One form, MDC1A, is the result of laminin alpha-2 deficiency and results in significant weakness, respiratory insufficiency and early death. Modification of apoptosis is one potential pathway for therapy in these patients.Methods:dy2J mice were treated with vehicle, 0.1 mg/kg or 1 mg/kg of omigapil daily via oral gavage over 17.5 weeks. Untreated age matched BL6 mice were used as controls. Functional, behavioral and histological measurements were collected.Results:dy2J mice treated with omigapil showed improved respiratory rates compared to vehicle treated dy2J mice (396 to 402 vs. 371 breaths per minute,

Outcome measures for BL6 control and vehicle treated dy^2J mice at 30–33 weeks of age show decreased activity, in vitro force and fibrosis.

*<p>Non-parametric comparison of medians; data expressed as mean ± SD; median (range).</p><p>Abbreviations: %FS – percent fractional shortening, %EF- percent ejection fraction, BPM- beats per minute, bpm – breaths per minute, SD – standard deviation, PA – pulmonary artery, AO – aortic, E/A – ratio of mitral valve E and A wave velocities, GSM – grip strength meter, BW- body weight, Gastroc – gastrocnemius, TA – tibialis anterior, KGF – kilogram-force.</p

Baseline outcome measures for BL6 control and dy^2J mice at 12–15 weeks of age show decreased body weights, forelimb grip strength, vertical activity and increased heart rates in dy^2J mice.

*<p>Non-parametric comparison of medians; data expressed as mean ± SD; median (range).</p><p>Abbreviations: %FS – percent fractional shortening, %EF- percent ejection fraction, BPM- beats per minute, Om – omigapil, SD – standard deviation, PA – pulmonary artery, Ao – aortic, E/A – ratio of mitral valve E and A wave velocities, GSM – grip strength meter, KGF – kilogram-force.</p