Revolutionary research in Catalonia
Scientists from IrsiCaixa and the Center de Regulació Genòmica (CRG) have managed to establish for the first time a connection between Down syndrome and certain mobile DNA fragments found in the genome of human beings, known as retrotransposons. These fragments have the unique ability to move through the genome and modify gene expression.
Study results
The new study reveals that, in the case of Down syndrome, retrotransposons operate abnormally. Several genes linked to neurological impairment have been found to be overexpressed, which could be contributing to the development of this condition. This phenomenon has been observed in analyzes carried out in Catalonia, where it has also been confirmed that lamivudine, an antiretroviral drug used against HIV, can regularize the expression of certain genes and, in this way, mitigate the activity of retrotransposons that favor the appearance of Down syndrome.
Previous publications and findings
The conclusions of this work have been published in the journal ‘Frontiers in Aging Neuroscience’. This research coincides with previous studies that showed an improvement in memory, motor activity and a reduction in anxiety after treatment with lamivudine. Retrotransposons, like viruses, can replicate and be reincorporated into other parts of the genome, thus altering gene expression, although they lack the capacity for infection.
The role of lamivudine
Lamivudine not only inhibits HIV replication, but also blocks the ‘copy and paste’ process characteristic of retrotransposons. The team of researchers has examined gene expression in brain tissues of preclinical models with Down syndrome, specifically in mice. It has been shown that many of these mobile DNA fragments are overexpressed, which causes dysfunctions in genes essential for proper neural functioning, with special emphasis on mouse chromosomes 16 and 17, homologous to human chromosome 21, which is altered in the Down syndrome.
Potential contributions to other neurological conditions
The study authors suggest that lamivudine could not only have applications in the treatment of Down syndrome, but also has the potential to slow the progression of Alzheimer’s disease and could be beneficial in preventing aging. This is because high expression levels have been observed in genes such as App, Ets2 and Olig2, which are related to the development of Alzheimer’s disease, cell death and disorders in neuronal development, respectively.
The future of research
The researchers believe that the results obtained point to a promising future for lamivudine in the treatment of neurological abilities and aging. This working group, which includes actors such as the Pasqual Maragall Foundation, the Center for Genomic Regulation, and the Alzheimer’s Unit of the Can Ruti Neurology Service, plans to continue in this direction and initiate a study in humans who are in the early stages of Alzheimer’s. Its objective is to evaluate markers present in plasma and cells to predict and analyze the effectiveness of the proposed treatments.