Method of early detection of duchenne muscular dystrophy and other neuromuscular disease
First Claim
1. A method of diagnosing or aiding in diagnosing of a perturbation of an autonomic nervous system in a subject, the method comprising the steps of:
- a) administering, into a body of the subject, an effective amount of a cholinergic agent or a derivative thereof; and
, b) determining whether the cholinergic agent or a derivative thereof, elicits a cholinomimetic effect in the subject, as opposed to a cholinergic effect, thereby identifying whether the subject has indications of the perturbation of the autonomic nervous system.
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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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Citations
30 Claims
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1. A method of diagnosing or aiding in diagnosing of a perturbation of an autonomic nervous system in a subject, the method comprising the steps of:
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a) administering, into a body of the subject, an effective amount of a cholinergic agent or a derivative thereof; and
,b) determining whether the cholinergic agent or a derivative thereof, elicits a cholinomimetic effect in the subject, as opposed to a cholinergic effect, thereby identifying whether the subject has indications of the perturbation of the autonomic nervous system. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method of diagnosing or aiding in diagnosing of Duchenne muscular dystrophy in a subject, the method comprising the steps of:
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a) administering, into a body of the subject, an effective amount of a cholinergic agent or a derivative thereof, and, b) determining whether the cholinergic agent or a derivative thereof, elicits a cholinomimetic effect in the subject, as opposed to a cholinergic effect. - View Dependent Claims (23, 24, 26, 27, 28, 30)
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25. A method for treating a heart-disorder state associated with dystrophin in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of one of a cholinergic agent, a muscarinic agent, an adrenergic agent, and a derivative thereof, such that treatment of heart-disorder state occurs.
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29. A method of diagnosing or aiding in diagnosing a subject suffering from a dystrophin-deficient disorder, or at risk of developing a dystrophin-deficient disorder comprising the steps of:
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a) administering topically into an eye of the subject an effective amount of one of a cholinergic, a muscarinic agent, and a derivative thereof, to induce a physiological change in the eye;
b) comparing a physiological change in the subject with a response under similar conditions in a normal subject, thereby identifying whether the subject suffers from dystrophin-deficient disorder.
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Specification