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A METHOD FOR TREATING HCMV IN VASCULAR DISEASE
Phone: (503) 626-1144
Email: JIM.HICKS@VIROGENOMICS.COM
Phone: (503) 626-1144
Email: JWKORFHAGE@AOL.COM
Cardiovascular disease remains the most common cause of death in the United States. While atherosclerosis accounts for the majority of these deaths, other vasculopathies such as restenosis after
coronary angioplasty, and transplant vascular sclerosis (TVS), the hallmark
lesion of chronic solid organ graft rejection, cause significant morbidity and
mortality. Clinical studies have directly associated human cytomegalovirus
(HCMV) with the acceleration of TVS and vascular restenosis foliowing
angioplasty and there is anecdotal evidence for an association with
atherosclerosis. Recent work by Virogenomics' founding scientists has shown
that HCMV infection of arterial, but not venous, smooth muscle cells (SMC)
results in significant cellular migration in vitro. Migration was found to be
dependent on expression of one of the four HCMV encoded chemokine receptors,
US28, and the presence of the chemokines RANTES or MCP-1. Virogenomics is
testing the hypothesis that blocking the expression or function of US28 can
relieve the negative effects of HCMV on vascular disease. In this Phase I
application we propose to test the effect of antisense molecules on the
expression of US28 and its mouse cognate, m33, and furthermore, to test whether
antisense treatment can block SMC migration in vitro. The Phase II goals will
extend this antisense strategy into animal models and eventually to initiate a
drug discovery program to identify small molecules blocking US28 function, with
the ultimate goal of developing human therapeutics for the viral component of
vascular disease.
* Information listed above is at the time of submission. *