An antiretroviral improves cognitive ability in mice with Down syndrome

A common antiretroviral drug used to treat HIV, lamivudine, improves cognitive ability in mice with Down’s Syndromeaccording to a study published today in the Journal of Cellular and Molecular Medicine.

The study was carried out at the Center for Genomic Regulation (CRG) and the IrsiCaixa AIDS Research Institute, in Barcelona (eastern Spain), which will now start a clinical trial to test it in humans.

The research highlights the potential of lamivudine, or other drugs capable of blocking the same therapeutic target, to improve cognitive impairment in Down syndrome, although the researchers admit that clinical studies still need to be done to confirm that the drug causes a similar effect in humans.

The Down’s Syndrome it is a condition caused by the presence of an extra chromosome in the human genome, which contains 23 pairs of chromosomes, but, in the case of people with this syndrome, there is one of these pairs that, instead of two, has three copies of chromosome number 21.

In addition to other problems, people with Down syndrome also have a higher risk of Alzheimer’s, since chromosome 21, which is tripled, contains the genes for a protein relevant to this disease, amyloid precursor protein (APP), which it accumulates in the brain generating protein aggregates that cause alterations in brain function.

These protein aggregates are common in most people over 40 years of age with Down syndrome, with no preventive treatment so far.

Now, the results of this study point to a possible route of treatment with drugs and place retrotransposons as a possible therapeutic target for Down’s Syndromeas explained by the director of IrsiCaixa, Bonaventura Clotet.

Retrotransposons are segments of DNA that change their location within the genome itself, creating RNA copies of themselves to leave the area of ​​the genome where they are located and become DNA again so that they can be re-inserted into the genome, but already in another place.

These segments can be inserted in specific areas of the genome and, by chance, position themselves in promoter regions of genes associated with neurodegenerative diseases, enhancing their activity.

According to Clotet, the activity of these DNA segments to jump from one place to another in the genome increases with age.

“In addition, retrotransposons have some similarities with HIV since, like this virus, they need to go from DNA to RNA, and vice versa, to make copies of themselves”, the specialist broke down.

In this way, the researchers hypothesized that the use of molecules capable of inhibiting HIV replication – 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 enzyme reverse transcriptase,” Clotet explained.

The scientific community had shown that lamivudine, an inhibitor of this enzyme that is already used against HIV, decreased the activation of retrotransposons in elderly mice, so they thought that its use could also be useful to counteract the associated cognitive impairment to Down syndrome.

To demonstrate this, mice with Down syndrome were treated with lamivudine for four months, while another group was used as a control and only received water.

They experimented with behaviors designed to test locomotor activity, recognition memory, and anxiety, and found that mice given lamivudine showed better cognitive abilities.

CRG researcher Mara Dierssen added that the results of the study raise the hypothesis that the benefits observed thanks to 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 offering them more options to live independently, in particular those affected by early-stage Alzheimer’s disease”Dierssen pointed out.

“We continue to need pharmacological treatments that consistently help improve memory, attention and language functions, or prevent cognitive decline associated with aging in people with Down syndrome”he added.

This studio “It is one more step to change this situation”since it reveals that the activity of retrotransposons is an interesting mechanism that needs to be studied not only in aging, but also in neurodevelopmental disorders.

The next step for the researchers is to start clinical trials with the drug in people with Down syndrome and Alzheimer’s disease.

Source: EFE