Got to Go? Harvard Scientists Find New Relief for
Urinary Incontinence, Overactive Bladder
New focus on proteins in cells lining the surface of
the bladder may lead to new drug relief for incontinence that affects millions of
Feb. 11, 2013 - If you have an overactive bladder
or urinary incontinence, help could be on the way. Most drug treatments today
target proteins in the muscle surrounding the bladder, but new research
shows that it may be possible to design drugs that target sensory
proteins in the epithelium, a thin layer of cells which line the surface
of the bladder.
The new research report published online in the
FASEB Journal, shows that
the this lining, the epithelium, is able to sense how full the bladder
is through the action of a family of proteins called integrins. As the
bladder becomes full, the cells in the epithelium stretch and become
thinner, which activates the integrins to send that information to
nerves and other cells in the bladder.
As a result of this new knowledge, researchers may
one day be able to design drugs that target this mechanism to treat
conditions like incontinence and overactive bladder, both of which are
common, serious, problems affecting millions of people.
"I am very hopeful that as we learn more about how
the bladder senses fullness and conveys that information to the nerves
and the muscles which control our ability to urinate, that this greater
understanding and knowledge will lead to new treatments," said Warren G.
Hill, Ph.D., a researcher involved in the work from the Department of
Medicine at Beth Israel Deaconess Medical Center and Harvard Medical
School in Boston, MA.
"It is extremely important that we do this as
quickly as possible, since there are millions of people who suffer
enormously from the anguish of bladder pain, incontinence and constant
feelings of needing to go."
Dr. Hill added, "I am optimistic these new insights into the
role of integrins will begin the process of discovering important new
drug targets which will dramatically improve the quality of life for
many of these people."
To make this discovery, Hill and colleagues tested
two groups of mice.
The first group were genetically modified to not
have an important member of the integrin family present in the
epithelium. These mice lacking the integrin protein had normal looking
bladders but very little urinary control.
The second group of mice was normal. These normal
mice also had normal looking bladders, but as expected, had bladder
Researchers then tested the bladders from the
integrin knockout mice and found that their bladders were constantly
squeezing and very overactive. In addition, they overfilled their
bladders and took much longer to urinate than the normal mice.
"No one wants to pee in his or her pants," said
Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but the
reality is that bladder problems – incontinence, frequency and pain -
affect more people than we realize. This report offers hope that new
drugs targeting the bladder's epithelium will succeed when current drugs
FASEB Journal is
published by the Federation of the American Societies for Experimental
Biology (FASEB). It is among the most cited biology journals worldwide
according to the Institute for Scientific Information and has been
recognized by the Special Libraries Association as one of the top 100
most influential biomedical journals of the past century.
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