(HealthDay News) — A small interfering RNA (ALN-PCS) that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) is safe and seems effective for lowering low-density lipoprotein (LDL) cholesterol, according to a phase 1 study published online Oct. 3 in The Lancet.

Kevin Fitzgerald, Ph.D., from Alnylam Pharmaceuticals in Cambridge, Mass., and colleagues conducted a placebo-controlled, phase 1 dose-escalation study involving 32 healthy adult volunteers with serum LDL cholesterol of 3.0 mmol/L or more. Participants were randomized to receive one dose of intravenous ALN-PCS (24 participants; doses ranging from 0.015 to 0.400 mg/kg) or placebo (eight participants).

The researchers found that a similar proportion of participants experienced a treatment-emergent adverse effect in the ALN-PCS and placebo groups (79 versus 88 percent). ALN-PCS was rapidly distributed and, across the dose range tested, the peak concentration and area under the curve increased in a roughly dose-proportionate manner. Treatment with 0.400 mg/kg correlated with a mean 70 percent reduction in circulating PCSK9 plasma protein and, relative to placebo, with a mean 40 percent decrease in LDL cholesterol from baseline.

“Our results suggest that inhibition of PCSK9 synthesis by RNA interference provides a potentially safe mechanism to reduce LDL cholesterol concentration in healthy individuals with raised cholesterol,” the authors write.

The study was funded by Alnylam Pharmaceuticals, the developer of ALN-PCS.

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