Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing
Reexamination Certificate
2005-04-05
2005-04-05
Wang, Shengjun (Department: 1617)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
C600S300000, C600S301000
Reexamination Certificate
active
06875418
ABSTRACT:
The mdx mouse is a model of Duchenne muscular dystrophy. The present invention describes that mdx mice exhibited clinically relevant cardiac phenotypes. A non-invasive method of recording electrocardiograms (ECGs) was used to a study mdx mice (n=15) and control mice (n=15). The mdx mice had significant tachycardia, consistent with observations in patients with muscular dystrophy. Heart-rate was nearly 15% faster in mdx mice than control mice (P<0.01). ECGs revealed significant shortening of the rate-corrected QT interval duration (QTc) in mdx mice compared to control mice (P<0.05). PR interval duration were shorter at baseline in mdx compared to control mice (P<0.05). The muscarinic antagonist atropine significantly increased heart-rate and decreased PR interval duration in C57 mice. Paradoxically, atropine significantly decreased heart-rate and increased PR interval duration in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart-rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. These electrocardiographic findings in dystrophin-deficient mice provide new bases for diagnosing, understanding, and treating patients with Duchenne muscular dystrophy.
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Lahive & Cockfield LLP
Mouse Specifics, Inc.
Wang Shengjun
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