Pioneering research on Down syndrome
A team of scientists from the IrsiCaixa institution and the Centre for Genomic Regulation has established for the first time a link between Down syndrome and mobile DNA elements, known as retrotransposons, which are present in the human genome. These retrotransposons have the ability to move along the genome and modify the expression of various genes, which may have significant implications for different pathologies.
Implications for gene expression
The study, carried out in Catalonia, reveals that in the case of Down syndrome, retrotransposons present abnormal expression. Specifically, it was possible to identify that certain genes linked to neurological deterioration are overexpressed, which may contribute to the appearance and development of this condition. This finding also suggests a possible therapeutic intervention through the use of lamivudine, an antiretroviral drug intended to combat HIV, which has been shown to have the ability to regulate the expression of some of these genes involved in Down syndrome.
Encouraging results in preclinical models
The research has recently been published in the journal ‘Frontiers in Aging Neuroscience’ and complements previous studies that recorded improvements in areas such as memory, motor activity and anxiety management after treatment with lamivudine in preclinical models. It has been proven that the functionality of retrotransposons is similar to that of certain viruses, since they have the ability to copy themselves and reinsert themselves in different areas of the genome without causing infections.
Lamivudine mechanism of action
In addition to inhibiting HIV replication, lamivudine works by stopping the ‘copy and insertion’ process that characterizes retrotransposons. When examining gene expression in brain tissues of mice serving as preclinical models of Down syndrome, notable overexpression of these mobile DNA fragments was observed, altering neuronal function. In mice treated with lamivudine, the normal expression of some genes that had been altered was restored.
Outlook for Alzheimer’s and aging
The researchers suggest that lamivudine could have broader applications, not only in Down syndrome, but also in preventing the progression of Alzheimer’s and the aging process. The data obtained indicate an overexpression of genes associated with Alzheimer’s and neuronal development, which reinforces the potential of the treatment.
Future of research
The multidisciplinary team, which includes the Pasqual Maragall Foundation and the Center for Genomic Regulation, plans to continue their research by carrying out a study in humans in the early stages of Alzheimer’s. In the future, they will seek to analyze markers in plasma and cells to predict and study the response to treatment, hoping to contribute to the advancement of effective therapies for these neuroscience-related conditions.