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Lamivudine, a commonly-used antiretroviral drug for treating HIV, improves cognition in a mouse model of Down syndrome, according to the findings of a joint new study by researchers at the Centre for Genomic Regulation (CRG) and the IrsiCaixa AIDS Research Institute, a centre jointly promoted by the “la Caixa” Foundation and the Department of Health of the Generalitat de Catalunya. The research is published today in the Journal of Cellular and Molecular Medicine.
Though clinical studies are necessary to confirm that the drug elicits a similar effect in humans, the initial research highlights the potential of using pharmacological interventions such as lamivudine — or other drugs capable of blocking the same therapeutic target — as a treatment for ameliorating cognitive impairment of people with Down syndrome.
Down syndrome is a condition in which a person has an extra chromosome. Typically, a baby is born with 46 chromosomes. Babies with Down syndrome have an extra copy of one of these, the 21st chromosome. This results in mild to moderate intellectual disability, diclofenac sodium for fever affecting general cognition traits such as memory, attention span and speaking ability. Adults with Down syndrome also experience accelerated aging, resulting in relatively rapid cognitive decline more commonly seen in much older adults in the general population.
People with Down syndrome are also at increased risk of Alzheimer’s disease. Chromosome 21 plays an important role in this relationship as it carries a gene — amyloid precursor protein (APP) — that produces amyloid proteins that build up in the brain and are associated with disrupting brain function. Amyloid accumulation is common in most adults over the age of 40 with Down syndrome.
To aid independent living, most people with Down syndrome undergo psychosocial interventions such as cognitive stimulation therapy, one of the only treatment options currently available. However, no pharmacological interventions exist to date. Targeting retrotransposons is a new unexplored option for Down syndrome that this work demonstrates is of great therapeutic interest.
Retrotransposons are segments of DNA that change their location within the genome by making RNA copies of themselves that jump back into DNA at another location. Retrotransposons can insert themselves into specific areas of the genome and, by chance, position themselves in gene-promoting regions associated with neurodegenerative diseases, enhancing their activity. Rates of retrotransposition increase with age and cellular senescence.
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