Urinary incontinence is a common condition that is a frequent cause of confinement to nursing homes among the elderly. It afflicts significant numbers among both men and women of all ages. Urinary incontinence is believed to currently affect over 12 million people in the United States alone, and to occur in between 15 and 30% of the population over the age of 60. In addition, studies show some degree of daily incontinence reported among as many as 17% of young, apparently healthy women.
Urinary incontinence is a manifestation of the failure to control the muscles of the bladder or urinary sphincter. Incontinence results when the pressure within the bladder is too great as a result of excessive force exerted by the bladder muscles, or when the sphincter muscles are too weak. Urinary incontinence can be a manifestation of other diseases such as Parkinsonism, multiple sclerosis, lesions of the central nervous system, or bladder infections. Interstitial cysts can result in instability of the bladder detusor muscles and a particularly unpleasant form of urge incontinence.
Current treatments for urinary incontinence rely on the control of G protein coupled receptors (GPCR) of the muscarinic class. These GPCR proteins are intracellular proteins that act as transducers of binding by extracellular ligands to cell surface G protein coupled receptors (“GPCRs”). Zhong and Neubig, 2001, Perspectives in Pharmacology 297:837-845, and the references cited therein, provide a review of GPCRs and their functions. Modulation of the signaling pathways downstream of the muscarinic GPCR's is responsible for proper muscle contraction within the bladder, and antagonists of these receptors have been utilized for this purpose, but have problems with specificity and side effects do to a lack of specificity.
The current standard of care is quite unsatisfactory. All of the current drugs now utilized to treat urinary incontinence suffer from polypharmacology and unwanted side effects. Safe and reliable methods and compounds are needed to improve the treatment and/or prevention of conditions involving defects in muscle contraction or the control of muscle contraction with one such example being urinary incontinence.
USPTO Backgrounds
USPTO Backgrounds