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GIGA-Cardiovascular researchers identify and solve a major side effect of cancer and cholesterol treatments
In last November, Cécile Oury and her team have shown that CpG oligodeoxynucleotides (CpG ODN, small DNA molecules used in numerous cancer therapies) activate blood platelets (that greatly increases the risk of thrombotic accident) and identify potential inhibitory strategy with a drug available on the market, which completely cancels this effect and the inherent risks (J Thromb Haemost. 2017 May;15(5):983-997).
Recently, Cécile Oury and Patrizio Lancellotti, head of the cardiology department of the University Hospital of Liège and director of the GIGA-Cardiovascular Sciences Unit published a letter in “The New England Journal of Medicine” where they explain that therapeutic RNAi carrying the same phosphorothiate modification as CpG ODN molecules could increase the risk of cardiovascular events in patients.
Everyone knows that high cholesterol levels increase the risk of cardiovascular disease. Statins, inhibitors of the enzyme that controls the synthesis of cholesterol, are widely used to treat excess cholesterol and are among the best-selling drugs in the world (there are 220 million patients worldwide). Nevertheless, their efficacy and safety is currently controversial. Pharmaceutical companies have therefore started to develop new treatments with targets other than statins. Recently, one of them has developed an RNAi that inhibits the synthesis of PCSK9 protein and thus has a significant effect on the decrease of LDL cholesterol, known to be the “bad” cholesterol. This drug, still experimental today, is called inclisiran.
Cécile Oury and Patrizio Lancellotti have published this warning because this new treatment is also likely, in the same way as CpG ODN… even though the initial goal is to reduce this risk. The clinical tests carried out before the release of this drug took into account the decrease of the count platelet but the 2 researchers of the GIGA warn the pharmaceutical industry by signaling to them that that is not enough and that one must also include tests on the Platelet activation in clinical trials. It is easy to understand that this precaution is even more important in hypercholesterolemic patients in whom the cardiovascular risks are already increased tenfold. Cecile and Patrizio will be involved in a major clinical trial on inclisiran in the context of cardiovascular disease.
In collaboration with a team at the University of California at Los Angeles (UCLA), researchers from GIGA-Neurosciences have discovered a new gene responsible for a seizure syndrome called juvenile myoclonic epilepsy (JME). This discovery was made as part of an international consortium that studies genetic abnormalities responsible for epileptic diseases. It is being published this week in
The LIGHTSHEET MICROSCOPY can deliver optical sections, 3D reconstructions and timelapse movies of whole sample volumes at subcellular resolutions. The fast scan speeds and low phototoxicity of the lightsheet allow to record the development of fluorescent transgenic animals over long time periods, such as zebrafish embryos. Alternatively 3D reconstructions of fixed whole organs or whole embryos,
The researchers discovered that this cellular dialogue controls the growth of the cerebral cortex and that its impairment leads a cortical malformation previously associated with autism in mice . Their results are published in the prestigious scientific journal Cell. The cerebral cortex contains excitatory and inhibitory interneurons. The former are produced locally and move by