Thousands of men are afflicted with an embarrassing and painful
condition that triggers spontaneous, long-lasting erections. There
are limited treatment options, but a solution could be on the way
thanks to new research at The University of Texas Health Science
Center at Houston.
Priapism is a condition of persistent painful penile erection in
the absence of sexual desire. It is highly associated with sickle
cell disease, leukemia and other blood disorders. It can also
result from vasoactive drug abuse. One of the most dangerous
complications seen in priapic patients is penile fibrosis, which
can lead to erectile dysfunction. Priapism can be an urgent
urological condition and causes of the erections lasting at least
four hours are unknown.
Biochemists in the laboratory of Yang Xia, M.D., Ph.D., an
associate professor at The University of Texas Medical School at
Houston, report that an FDA-approved drug called polyethylene
glycol-linked adenosine deaminase (PEG-ADA) relieved symptoms and a
major complication in a pre-clinical study. Current findings appear
online and will be in the March 2010 print issue of The FASEB
Journal, the journal of The Federation of American Societies
for Experimental Biology.
Xia believes priapism is linked to elevated levels of a
signaling molecule called adenosine. The link was discovered by Xia
and her colleagues when they noticed that genetically-deficient
mice with elevated levels of adenosine also had spontaneous
erections lasting many hours. Xia's team described their unexpected
finding last year in a paper published in The Journal of Clinical
Investigation. Subsequent work from this group has appeared in two
articles published in The Journal of Sexual Medicine.
"In this latest study, we show in mouse models that we can
prevent a major complication of priapism called penile fibrosis,
which is scarring of the penis and can lead to erectile
dysfunction," Xia said. "We built on our earlier work, which showed
that we can prevent and treat priapism in mouse models."
Mice were treated with PEG-ADA, a drug typically prescribed for
patients with a deficiency of the adenosine deaminase enzyme, which
degrades adenosine to maintain its normal levels. ADA deficient
people have a condition called Severe Combined Immunodeficiency
Disease (also known as SCID or the "Bubble Boy Disease") and are
treated with PEG-ADA, which replaces the missing enzyme.
PEG-ADA was associated with reduced penile fibrosis in one set
of mice with sickle cell disease features and in a second set with
a deficiency of the ADA enzyme. No serious side effects were
reported. "The next step could involve clinical trials," Xia said.
"Because the drug has already been approved for use in people with
SCID, the FDA approval process could be expedited."
Harinder Juneja, M.D., director of both the Division of
Hematology at the UT Medical School at Houston and clinical
hematology at Memorial Hermann - Texas Medical Center, said there
are limited treatment options for his male sickle cell patients
with priapism. "The main treatments are pain control, hydration and
surgical intervention," Juneja said. Male sickle cell patients have
about a 40 percent chance of getting priapism. "A medication that
could prevent the advent of priapism or treat established priapism
is definitely needed. "
"Taken together, substantial evidence now suggests a general
role for adenosine signaling in normal penile erection as a
vasorelaxant and neuromodulator," Xia said. "From this perspective
it is not surprising that impaired adenosine signaling is
associated with erectile dysfunction and excessive adenosine
signaling is associated with priapism."
SOURCE