New
approaches to endometriosis treatment – mouse
experiments point the way
Two new experimental
studies were presented at the 23rd meeting of ESHRE.
Both use mouse models to target angiogenesis, which
may play a role in endometriosis and thus provide novel
potential treatments of the disease.
LYON, 3 JULY
2007
Possible new directions for the treatment
of endometriosis, were outlined in the presentation
of two experimental studies at the 23rd annual conference
of the European Society of Human Reproduction and Embryology
today. Both concern targeting angiogenesis – the
formation of new blood vessels – which is encourages
endometriosis by providing a rich blood supply.
Dr. Edurne Novella-Maestre and colleagues
from the Valencia Infertility Institute (IVI), Spain,
studied Vascular Endometrial Growth Factor (VEGF), which
is known to be particularly involved in the angiogenesis
process and therefore in the development of endometriosis.
They created an experimental model of endometriosis
in nude mice in order to test whether dopamine agonists,
much used in other infertility treatment such as the
prevention of ovarian hyper-stimulation syndrome, could
be a new strategy for inhibiting endometrial lesions.
“We know that dopamine agonists are a safe treatment,
and that they have been used for many years in order
to stop breastfeeding, for example, without any major
side effects”, says Dr. Novella-Maestre, “so
we decided to see what effect they would have on the
experimental mice.”
The scientists found that the blood
vessel formation in the lesions was significantly decreased.
“The percentage of new blood vessels in the two
treatment groups was reduced in comparison to the control
group, and we also found that the percentage of old
blood vessels in these groups were higher”, says
Dr. Novella-Maestre. “The total number of the
blood vessels was not dissimilar in the treatment and
control groups, but the ratio of new/old blood vessels,
the numbers of cells growing in the endometrial area,
and the area lesions were totally different, suggesting
that there was inhibition of blood vessel replacement
in the treatment group.”
The team now intends to follow up the work in humans.
“Our initial experiments have confirmed the presence
of the dopamine receptor in human endometriosis, and
therefore we believe that treatment with dopamine agonists
will have the same effect on humans as it does on mice”,
she says. “This is encouraging, since current
therapies are still associated with a high recurrence
rate, and many of them can only be used for a limited
time due to unacceptable side effects and/or osteoporosis.
For women with pain, surgery can provide a temporary
relief, although symptoms recur in up to 75% of women
within two years. A long-term, safe, and non-invasive
solution is badly needed.”
An additional advantage of such a treatment,
say the scientists, is that it is likely that women
with endometriosis also have an increased risk of various
cancers. The simultaneous occurrence of endometriosis
with ovarian cancer, for example, suggests that endometriosis
constituents may transfer into tumour cells. “If
we are able to inhibit angiogenesis in the ectopic human
endometrium with a dopamine agonist”, says Dr.
Novella-Maestre, “we may be able to decrease the
cancer risk for these patients.”
In another presentation to the conference,
Dr. Ofer Fainaru, from Harvard Medical School and Children’s
Hospital Boston, USA, announced that his team has found
that dendritic cells – highly specialised immune
cells – support angiogenesis by enhancing blood
vessel growth. Using a mouse model of endometriosis,
they found that these cells incorporate into the endometriosis
lesions and enhance their growth. “We also found
that these cells have a similar effect on intra-abdominal
tumours”, he said.
“We therefore believe that targeting
dendritic cells may prove to be a promising strategy
for treating conditions dependent on angiogenesis, such
as endometriosis and cancer,” says Dr. Fainaru.
“Our next step will be to look for specific dendritic
cell inhibitors that could have the potential to decrease
angiogenesis in these conditions.”
The team hopes that in the future
it may be able to develop cell-specific therapy for
angiogenesis-dependent diseases that will be more effective
and less toxic than current treatments.
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