Molecular Therapy Is Designed to Protect Patients from Heart Attacks and Strokes

Already the unique therapy with a ribonucleic acid - a "small-interfering RNA" (siRNA) - protects patients with a high risk for cardiovascular diseases permanently against increased LDL cholesterol, a major risk factor for heart attack and stroke. This is the result of a clinical study carried out by scientists from the Charité - Universitätsmedizin Berlin and the Berlin Institute for Health Research together with the German Center for Cardiovascular Research (DZHK) and colleagues of Imperial College London. The study is published in the current issue of the New England Journal of Medicine *.

heart attacks

As a component of cell walls and as a building block of many hormones, the fat molecule cholesterol plays an important role in cell metabolism. However, if there is too much cholesterol in the blood, the risk of vascular limes and diseases such as myocardial infarction or stroke increases. High-risk patients who are suffering from very high LDL cholesterol values ​​due to an inherited disease are particularly at risk. In these patients, a protein with the acronym PCSK9 (proprotein-convertase subtilisin / kexin type 9) prevents the liver from removing the LDL cholesterol from the blood.

Scientists around the two first authors, Prof. Ulf Landmesser, Director of the Clinic for Cardiology at the Charité campus Benjamin Franklin and Prof. Kausik Ray from Imperial College London, used the principle of so-called RNA interference (“small interfering RNA” ), A cell mechanism that was discovered a few years ago and can effectively eliminate harmful proteins in the body. If double-stranded siRNA enters the cell, it is bound by a specific complex (RISC complex). This can be used for gene muting.

In their study, the researchers therefore investigated the efficacy and efficiency of siRNA against the protein PCSK9. A total of 501 high-risk patients with elevated LDL cholesterol values ​​received either different doses of the active substance inclisiran or a placebo subcutaneously. It was shown that inclisiran significantly reduced the amount of protein as well as the LDL cholesterol levels, the latter up to 41.9 per cent after a single dose and up to 52.6 per cent after a double dose.

“The long-lasting effect of treatment, which has been visible for nine months after a single dose, is particularly interesting for us”; Prof. Ulf Landmesser comments on the results of the study. “The next step is to further develop the treatment in a major clinical trial program as a new therapy to prevent heart attack and stroke in high-risk patients,” he adds.

* Original publication:

Ray KK, Landmesser U, Ladder LA, Kallend D, Dufour R, Karakas M, Hall T, Troquay RP, Turner T, Visseren FL, Wijngaard P, Wright RS, Kastelein JJ. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. N Engl J Med. 2017 Mar 17. doi: 10.1056 / NEJMoa1615758. [Epub ahead of print] PubMed PMID: 28306389.