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Oct 16, 2014
 |  BC Innovations  |  Targets & Mechanisms

Alnylam interrupts preeclampsia

Preeclampsia often involves overactivation of the renin-angiotensin system that regulates blood pressure, but inhibiting the pathway is not possible because it would be toxic to the fetus. Alnylam Pharmaceuticals Inc. has developed an siRNA conjugate that does not cross the placenta or affect fetal development but can block angiotensin signaling and improve symptoms in a rat model of the condition.

Preeclampsia occurs in about 5% of pregnant women and can lead to life-threatening seizures. The condition is usually diagnosed in the second or third trimester when symptoms of hypertension and proteinuria appear, but the precise etiology of preeclampsia is poorly understood.

Over the past 20 years, multiple studies have shown that preeclampsia and other forms of pregnancy-related hypertension often involve upregulation of the renin-angiotensin system caused by activating mutations in angiotensinogen (AGT)1-3or by agonistic autoantibodies that target a key receptor in the pathway called angiotensin II type 1 receptor (AGTR1).4,5 AGT, a protein produced mainly in the liver, sits atop a cascade that regulates angiotensin-converting enzyme (ACE)-induced production of the hypertensive peptide angiotensin II.

Many companies market antihypertensives that inhibit AGTR1 or ACE, but the drugs' use during pregnancy is contraindicated because they can cross the placental barrier and cause fetal injury or death.

Thus, the standard of care for preeclampsia involves managing symptoms by treating hypertension with other drug classes-such as calcium channel blockers and adrenergic receptor antagonists-in addition to using magnesium sulfate to prevent seizures and steroids...

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