Antiretroviral Drug Enhances Cognition in Mouse Model: Study

Lamivudine, a commonly-used drug for HIV increases cognition in a mouse model of Down syndrome, as per the new study.

Lamivudine, a commonly-used drug for HIV increases cognition in a mouse model of Down syndrome, according to the new study published in the Journal of Cellular and Molecular Medicine.

Initial research highlights the potential of using pharmacological modes like Lamivudine as treatment for decreasing cognitive impairment of patients with Down syndrome.

‘Targeting retrotransposons can be novel unexplored approach for Down syndrome. Lamivudine's efficacy in improving cognitive function is due to it's impact on the APP gene.’
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Down syndrome is a condition in which a person has an extra chromosome. Normally a baby will be born with 46 chromosomes, but a baby Babies with Down syndrome will have an extra copy of chromosome 21.

This causes mild to moderate intellectual disability, 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.

Most people with Down syndrome undergo psychosocial therapies like cognitive stimulation therapy. But, no pharmacological interventions exist to date. Targeting retrotransposons can be a novel unexplored option for Down syndrome.

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 retro transposition increase with age and cellular senescence.

Retrotransposons show some similarities to HIV, rapidly replicating within cells, though not necessarily with pathological implications. Hypothesis is that existing inhibitors that currently target the replication of HIV – such as the enzyme reverse transcriptase – could also work to block retrotransposons.

"Both HIV and retrotransposons need the same molecule to make copies of themselves: the reverse transcriptase enzyme," explains Dr. Bonaventura Clotet, Director of IrsiCaixa, Spain.

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“We know that Lamivudine, a reverse transcriptase inhibitor used against HIV, was shown in aged mice to decrease the activation of retrotransposons which could be linked to age-associated disorders.

Therefore, we thought that it could be useful to counteract the cognitive impairment associated with Down syndrome," he adds.

The researchers used Ts65Dn mice, the most widely-studied Down syndrome animal model to date. Mice were treated with Lamivudine for a period of four months, with another control group receiving water. The researchers then carried out various behavioral experiments designed to test locomotor activity, recognition memory and anxiety.

Effect of Lamivudine:

They found that mice receiving lamivudine showed improved cognition. The authors of the study hypothesize that the observed benefits of Lamivudine could be due to its effect on one or more variants of the APP gene.

“Our work aims to support people with Down syndrome and their families by providing them more options to live independent lives, particularly those affected by early-stage Alzheimer’s disease”, says Dr. Mara Dierssen, researcher at the CRG and co-author of the study.

“We still need pharmacological treatments that consistently help improve memory, attention and language functions, or prevent cognitive decline associated with ageing.

This study is one step aiming to change that, revealing retro transposition as an interesting mechanism to pursue not only in ageing but also in neurodevelopmental disorders,” concludes Dr. Dierssen.

Lamivudine is a medicine approved by the United States and European Union medical authorities for treating HIV infection. The researchers next plan to initiate clinical trials with the drug for people with Down syndrome and Alzheimer’s disease.

Source-Medindia