Lamivudine, the HIV drug that can revolutionize Down syndrome

Lamivudine, the HIV drug that can revolutionize Down syndrome

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Down syndrome, a disease where one has an extra chromosome 21, results in a set of symptoms characterized by a mild or moderate disability and an affectation of cognitive traits such as memory, attention or even speech. In addition, it is known that this syndrome accelerates aging, further exacerbating cognitive deterioration. Therefore, being able to alleviate some of these symptoms would improve the quality of many people, since only in Spain it is known that up to 35,000 people suffer from it.

Now, a new study carried out by the Center for Genomic Regulation (CRG) and the IrsiCaixa AIDS Research Institute, promoted by the ‘La Caixa’ Foundation and the Department of Health of the Generalitat de Catalunya, would suggest that an antiretroviral drug used in HIV would improve cognition in Down syndrome.

The drug, known as lamivudine, is a commonly used medication to treat HIV. But, according to new work published in the Journal of Cellular and Molecular Medicine, it would also be a good option to improve the cognitive symptoms (lack of memory, attention and speech) of Down syndrome. At least, in a mouse model. In the future, it is hoped that these results will be confirmed in clinical studies in humans, but this is initial research that would highlight the use of these and similar drugs in Down syndrome.

[¿Es posible curar el síndrome de Down con medicamentos?]

People with Down syndrome are also known to be at increased risk of Alzheimer’s, as chromosome 21 plays a key role in this relationship by providing a gene to produce amyloid precursor protein, or APP, which ends up giving rise to amyloid proteins that accumulate in the brain and would be associated with the brain alterations of this type of dementia. In fact, amyloid buildup is very common in adults over the age of 40 with Down syndrome.

Today there are psychosocial interventions such as cognitive stimulation therapy to help people with Down syndrome lead an independent life, but there are no pharmacological interventions. In this case, targeting retrotransposons would be an unexplored option to ameliorate the syndromes of this syndrome.

Retrotransposons are segments of DNA that change their location within the genome by making RNA copies of themselves that return to the DNA in another location. They can insert themselves into specific areas of the genome and, by chance, position themselves in promoter regions of genes associated with neurodegenerative diseases, enhancing their activity. And this retrotransposition increases with age and cell aging.

The retrotransposons show similarities to HIV and they replicate rapidly within cells, although not always with pathological implications. Even so, those responsible for the current study raised the hypothesis of using inhibitors like those used against HIV replication, such as the enzyme reverse transcriptase, but in this case to block retrotransposons.

“A hopeful result”

In fact, as explained by Bonaventura Clotet, director of IrsiCaixa, both HIV and retrotransposons they need the same molecule to make copies of themselves, the aforementioned reverse transcriptase. And lamivudine is an inhibitor of this enzyme, and it has already been used in elderly mice to reduce the activation of retrotransposons that could be related to age-related disorders. For this reason, they thought that it could also work to improve the cognitive deterioration present in other areas, such as Down syndrome.

So the researchers used Ts65Dn mouse models, a Down syndrome model commonly used in studies. For four months, mice were treated with lamivudine, and another control group only received water. Subsequently, several behavioral experiments designed to assess motor activities, recognition memory, and anxiety were carried out.

According to the results of the study, the mice that received lamivudine improved their cognitionsomething that the researchers relate to an effect on one or more variants of the APP gene related to chromosome 21, although it is something that they cannot yet confirm.

As the researchers themselves indicate, this study is only a first step towards improving the cognitive symptoms associated not only with Down syndrome, but also with aging and other neurodevelopmental disorders. At the moment lamivudine is only approved as a treatment for HIV infection in the United States and the European Union, but clinical trials in humans are already being considered to check the potential of this drug both in people with Down syndrome and Alzheimer’s disease.

“This is a test in an animal model, which evaluates only one aspect of cognitive processing and, while it is far from being a definitive treatment for people with Down syndrome, yes it supposes a hopeful result“, explains Casto Rivadulla, a scientist at the Center for Advanced Scientific Research (CICA) of the University of A Coruña to the Science Media Centre.

“It shows the possibility of reversing very complex cognitive alterations, such as object recognition memory, when animals are treated with the reverse transcriptase inhibitor. It also shows a new potential therapeutic targetnot only for Down syndrome, but also for other neurodegenerative pathologies that must be explored, thus opening new lines of work”, he adds.

“These results are obtained using a drug, lamivudine, which is already approved for the treatment of HIV, which would speed up the start-up of clinical trials in patients since studies on safety, contraindications, etc., have already been carried out. “, it ends.

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