RNAi Remedy Lowers Cholesterol

A Phase 1 clinical trial demonstrates the safety and efficacy of an siRNA-based, cholesterol-lowering drug.

By | October 3, 2013

Structure of the PCSK9 proteinWIKIMEDIA, EMWA new therapy has shown promise for patients who take cholesterol-lowering statins but suffer the side effects of muscle pain and weakness. The results of a Phase 1 clinical trial published online today (October 3) in The Lancet demonstrated that delivery of an siRNA formulated in a lipid nanoparticle safely and effectively lowered LDL cholesterol.

Researchers at Alynylam Pharmaceuticals in Cambridge, Massachusetts, developed an siRNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that typically binds and degrades LDL receptors, thereby increasing the levels of circulating LDL cholesterol. The siRNA, dubbed ALN-PCS, works by preventing the production of PCSK9 protein. Study participants who received the highest dose of ALN-PCS showed a 70 percent decrease in circulating PCSK9 protein, and an average of a 40 percent reduction in LDL cholesterol. Additionally, these participants experienced only mild adverse effects, which were comparable to those experienced by participants who received a placebo.

An accompanying commentary on the clinical trial, written by John Burnett and Amanda Hooper who are both scientists from the University of Western Australia, identified shortcomings, such as the small study size (32 participants) and the lack of female participants (only eight were women). Burnett and Hooper also discussed potential for off-target effects with the siRNA treatment that might be avoided by the use of other developing techniques, such as injected anti-PCSK9 antibodies.

But some scientists pointed out that this trial, though small, still represents proof of principle that siRNA therapeutics may someday be effectively used to treat disease. “It’s among the first demonstrations of RNA interference working in humans in a safe and tolerable way,” cardiologist Jean-Claude Tardif of the Montreal Heart Institute in Canada, who was not involved in the study, told Nature. “It’s very exciting.”


Add a Comment

Avatar of: You



Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo


Avatar of: T S Raman

T S Raman

Posts: 35

October 4, 2013

Statins were also certified as being capable of "safely and effectively" lowering cholesterol, and only recently have the "side effects of muscle pain and weakness"  been discovered or acknowledged. So, how can one so quickly certify that the siRNA treatment is safe and effective?

A somewhat related question that arises in my mind is regarding a possible interaction between bisphosphonates (e.g. alendronate) and statins, both of which interfere with isoprenoid biosynthesis, and, therefore, mght have effects on biosynthesis of compounds like Coenzyme-Q, Corticosteroids, etc. Does this have anything to do with the side-effects of "muscle pain and weakness"? Is there any information available on this aspect? My question has relevance to the fact that bisphosphonates and statins are taken concomitantly by many, especially elderly, patients.


Popular Now

  1. Sex Differences in the Brain
    Features Sex Differences in the Brain

    How male and female brains diverge is a hotly debated topic, but the study of model organisms points to differences that cannot be ignored.

  2. DNA Repair Pioneers Win Nobel
    Daily News DNA Repair Pioneers Win Nobel

    Tomas Lindahl, Paul Modrich, and Aziz Sancar have won this year’s Nobel Prize in Chemistry for their work elucidating mechanisms of DNA repair.

  3. Antiparasite Drug Developers Win Nobel
    Daily News Antiparasite Drug Developers Win Nobel

    William Campbell, Satoshi Omura, and Youyou Tu have won this year’s Nobel Prize in Physiology or Medicine in recognition of their contributions to antiparasitic drug development.

  4. Brain Gain
    Features Brain Gain

    Young neurons in the adult human brain are likely critical to its function.

Drummond Scientific
Drummond Scientific
Life Technologies