Methods for prevention and treatment of gastrointestinal disorders

Abstract

Disclosed are methods for preventing or treating a gastrointestinal (GI) disorder in a mammal such as a human patient. In one embodiment, the methods include administering to the mammal a therapeutically effective amount of a compound that modulates a nitric oxide (NO) signaling pathway, particularly in GI neurons. Methods of the invention are particularly useful for the treatment (including prophylactic treatment) of diabetic gastropathies and other GI disorders.

Description

FIELD OF THE INVENTION The present invention generally relates to methods for preventing or treating gastrointestinal (GI) disorders. In one aspect, the invention provides methods for treating the disorders by modulating nitric oxide (NO) signaling pathways particularly in GI neurons. Methods of the invention typically involve administering at least one compound that modulates the pathway by increasing one or more of NO activity or levels of neuronal nitric oxide synthase (nNOS). The invention has a wide spectrum of useful applications including treating a variety of gastropathies by administering a therapeutic amount of at least one of insulin or a phosphodiesterase (PDE) inhibitor. BACKGROUND OF THE INVENTION Hypomotility is one feature of a wide spectrum of gastrointestinal (GI) disorders. For example, gastric hypomotility accompanied by delayed emptying has been described. Stasis impacting the intestine, for example, is also known. See generally McCallum, R. W. (1989) in GASTR...

AI Technical Summary

Benefits of technology

We have discovered that by modulating NO signaling pathways in GI neurons it is possible to prevent or treat a wide spectrum of disorders. In particular, it has been found that particular NO signaling pathways are damaged in many mammalian GI disorders. Preferred invention methods generally prevent or treat such disorders by enhancing activity of certain identified molecules in the pathway, typically the NO molecule or the enzyme that facilitates production of that molecule ie., the nNOS enzyme. Preferred invention methods suitably increase and more preferably restore normal neuronal NO signaling, thereby helping to prevent, reduce the severity of, or eliminate symptoms associated with many GI disorders.

The foregoing general invention method suitably modulates the NO signaling pathway. More particularly, the method provides, for the first time, a way of therapeutically amplifying this important pathway in the presence of abnormal levels of NO or nNOS enzyme. Thus, the method beneficially provides to “at risk” or diseased GI neurons at least one of increased NO activity or increased levels of the nNOS enzyme. This important invention feature desirably increases and preferably restores NO signaling typical of normal GI neurons. Additionally, the methods of the invention may provide supra-physiologic (higher than normal) levels of NO, nNOS, cGMP, etc. which can have important therapeutic benefits, for instance in the treatment of irritable bowel syndrome and other disorders. Without being bound by any theory, by such actions, the GI disorder thus can be prevented or treated by practice of the method.

Problems solved by technology

In particular, it has been found that particular NO signaling pathways are damaged in many mammalian GI disorders.

Without wishing to be bound to theory, that loss of key signaling components is thought to negatively impact a wide variety of cell functions important for normal GI function.

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