RNA vs mutation
Biologists have created the first RNA cure for Charcot-Marie–Toute disease
Scientists have developed a short RNA molecule that can be used to stop Charcot–Marie–Toute disease, due to which people gradually lose mobility. Thanks to this molecule, mice were able to get rid of the symptoms of this disease for several weeks.
The results of the study were published by the scientific journal Communications Biology (Boutary et al., Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A).
"Experiments on mice have shown that RNA injections very quickly restored the mobility of mice and returned their muscles to their former strength. For the severe form of Charcot–Marie–Toute disease, it lasted about three weeks, for the mild – about ten," the researchers write.
Charcot–Marie–Toute disease, also known as hereditary motor-sensory neuropathy, is a hereditary neurodegenerative disease that affects on average one person out of 2.5 thousand. It occurs due to the fact that mutations occur in those parts of the genome that are responsible for the assembly of various protein molecules in peripheral motor neurons.
As a result, the myelin sheath that covers these nerves is gradually destroyed. Therefore, carriers of this syndrome lose mobility of the arms, legs and other parts of the body. Until recently, there was not a single working method of treating Charcot–Marie–Toute disease, so most of its carriers are doomed to disability.
French scientists led by the director of the laboratory of the National Institute of Medical Research of France, Lilian Massadet, have created the first prototype of a drug for one of the most common forms of Charcot–Marie–Toute disease, which is associated with a mutation in the PMP22 gene.
This section of DNA is responsible for the production of the protein of the same name – one of the most important components of the myelin sheath of nerves, which can be compared to insulation on electrical wires. If mutations occur in PMP22, then neurons begin to produce too many molecules of this protein. This, in turn, leads to serious disorders in the work of the myelin sheath of nerve cells and Charcot–Marie–Toute disease.
Massade and her colleagues suggested that such disorders can be suppressed with the help of short RNA molecules that can connect with copies of PMP22 in the cytoplasm of neurons and prevent cellular protein "factories" from reading them. The first experiments showed that such strands of RNA worked well in cell cultures, but when injected into the body of experimental animals, they were quickly destroyed.
Scientists solved this problem by placing strands of RNA inside nanoparticles that consist of squalene, a hydrocarbon that is present in some vegetable oils and shark liver. Chemists have recently found out that squalene molecules can combine into hollow nanostructures that can penetrate into living cells and gradually dissolve in them.
Having packed many short RNA molecules into such nanoparticles, the scientists tested their work on genetically modified mice. In the PMP22 gene of these animals, the researchers introduced approximately the same mutations that are usually found in carriers of Charcot–Marie–Toute disease. Experiments have shown that the experimental drug relieved rodents of all symptoms of the disease for several weeks.
Massade and her colleagues note that after their success, preclinical and clinical trials with human participation can begin. Scientists hope that these experiments will end just as successfully, which will pave the way for the creation of the first full-fledged methods of treating Charcot–Marie–Toute disease.
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