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Common drug could counter cognitive decline in Down syndrome

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The news that you will read next speaks of a scientific advance that, for the moment, it has only shown its success in mice. It is good to make this premise clear when talking about a discovery that somehow opens a gap of hope for many. That said, here goes one of the most relevant scientific news of the day. A new study in rodents suggests that the use of lamivudinea commonly used antiretroviral to treat people with HIV, could counteract cognitive decline associated with Down syndrome. In other words, a pill already studied and authorized by the health authorities to deal with a virus shows, for now, promising results against other types of genetic disorders.

The research, still in the preclinical phase, suggests that this drug could be used as a ‘therapeutic target’ for block one of the proteins that cause the accelerated aging that affects people with this genetic disorder and that, on many occasions, increases the risk of Alzheimer’s in these patients. As explained by the researchers responsible for this study, from the Center for Genomic Regulation (CRG) and the IrsiCaixa Institute, the first tests in mice suggest that this treatment could also improve other cognitive skills as the memory, attention and language.

The hypotheses behind the operation of this drug in patients with Down syndrome is as follows. The Down’s Syndrome is a genetic condition caused by the presence of an extra copy of chromosome 21. This extra chromosome contains, in turn, the genes for those known as amyloid precursor proteins (APPs) that can accumulate in the brain and cause alterations in brain function. How and when does the accumulation of these proteins begin? This phenomenon has to do with retrotransposons: segments of DNA that change their location within the genome itself and that, on occasion, can stimulate the activity of regions associated with neurodegenerative diseases.

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As the experts explain, these ‘jumps’ of the retrotransposons and the accumulation of proteins are more frequent with increasing age of the patient. In fact, the symptoms of cognitive impairment caused by this phenomenon are a very common trait in most individuals over 40 years of age with Down syndrome. Having clarified how this mechanism develops, the researchers set out to study what would happen if were able to inhibit the replication of genetic elements causing this process with a drug commonly used to treat patients with HIV.

experimental study

The experiment, whose results are published this Tuesday in the scientific journal ‘Journal of Cellular and Molecular Medicine’, was developed as follows. The scientific team took as a reference a group of genetically modified rodents to study Down syndrome. The animals were divided into two groups. The first received lamivudine for four months. The second received only water as a ‘placebo’. At the end of this period, the researchers carried out several experiments to monitor the condition of the animals and observed that those who had taken the antiretroviral showed better cognitive abilities That the others. This, according to the experts, would suggest that lamivudine could have beneficial effects on one or more variants of the APP gene.

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As explained by Dr. Bonaventura Clotetdirector of IrsiCaixa, both HIV and retrotransposons need the same molecule to make copies of themselves: the reverse transcriptase enzyme. Previous studies had pointed out that the drug known as lamivudine, an inhibitor of this enzyme that is already used against HIV, also decreased the activation of retrotransposons in aged mice. “That is why we think that the use of lamivudine could also be useful for counteract cognitive impairment associated with Down syndromesays the scientist.

This treatment, for now, it has only been shown to be effective in animal models. Specifically, in rodents. But as the researchers explain, the next step in the investigation will be test this drug in a clinical trial with patients with Down syndrome and Alzheimer’s. “Our work aims to support people with Down syndrome and their families by offering them more options to live independentlyin particular to individuals affected by Alzheimer’s disease in the initial phase”, emphasizes Dr. Mara Dierssen, a researcher at the Center for Genomic Regulation (CRG), in relation to the possible future applications of this discovery.

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