Lamivudine, a reverse transcriptase inhibitor, rescues cognitive deficits in a mouse model of down syndrome

Martínez de Lagrán Cabredo, María; Elizalde-Torrent, Aleix; Paredes, Roger; Clotet, Bonaventura; Dierssen, Mara

doi:http://dx.doi.org/10.1111/jcmm.17411

Lamivudine, a reverse transcriptase inhibitor, rescues cognitive deficits in a mouse model of down syndrome

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Martinez de Lagran M, Elizalde-Torrent A, Paredes R, Clotet B, Dierssen M. Lamivudine, a reverse transcriptase inhibitor, rescues cognitive deficits in a mouse model of down syndrome. J Cell Mol Med. 2022 Aug;26(15):4210-5. DOI: 10.1111/jcmm.17411

Abstract

An elevated activity of retrotransposons is increasingly recognized to be implicated in a wide range of neurodegenerative and neurodevelopmental diseases. Down syndrome (DS) is the most common genetic disorder associated with intellectual disability and a genetic form of Alzheimer's disease. For this reason, we hypothesized that treatment with reverse transcriptase inhibitors could ameliorate DS phenotypes. In this proof of concept study, we treated trisomic (Ts65Dn) mice, a model of DS, with lamivudine, a reverse transcriptase inhibitor. We detected a significant improvement of neurobehavioural phenotypes, and a complete rescue of the hippocampal-dependent recognition memory upon treatment with lamivudine. Despite clinical studies in patients with DS are warranted, this study lays the groundwork for a novel and actionable therapeutic approach.