RT Journal Article
T1 Early Treatment with Metformin Improves Neurological Outcomes in Lafora Disease
A1 Burgos, Daniel
A1 Machío-Castello, María
A1 Iglesias-Cabeza, Nerea
A1 Giráldez, Beatriz
A1 González Fernández, Juan
A1 Sánchez-Martín, Gema
A1 Sánchez, Marina
A1 Serratosa, José
AB Lafora disease is a fatal form of progressive myoclonic epilepsy caused by mutations in the EPM2A or NHLRC1/EPM2B genes that usually appears during adolescence. The Epm2a−/− and Epm2b−/− knock-out mouse models of the disease develop behavioral and neurological alterations similar to those observed in patients. The aim of this work is to analyze whether early treatment with metformin (from conception to adulthood) ameliorates the formation of Lafora bodies and improves the behavioral and neurological outcomes observed with late treatment (during 2 months at 10 months of age). We also evaluated the benefits of metformin in patients with Lafora disease. To assess neurological improvements due to metformin administration in the two mouse models, we evaluated the effects on pentylenetetrazol sensitivity, posturing, motor coordination and activity, and memory. We also analyzed the effects on Lafora bodies, neurodegeneration, and astrogliosis. Furthermore, we conducted a follow-up study of an initial cohort of 18 patients with Lafora disease, 8 treated with metformin and 10 untreated. Our results indicate that early metformin was more effective than late metformin in Lafora disease mouse models improving neurological alterations of both models such as neuronal hyperexcitability, motor and memory alterations, neurodegeneration, and astrogliosis and decreasing the formation of Lafora bodies. Moreover, patients receiving metformin had a slower progression of the disease. Overall, early treatment improves the outcome seen with late metformin treatment in the two knock-out mouse models of Lafora disease. Metformin-treated patients exhibited an ameliorated course of the disease with slower deterioration of their daily living activities.
PB Elsevier
SN 1933-7213
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/94060
UL https://hdl.handle.net/20.500.14352/94060
LA eng
NO Burgos, D.F., Machío-Castello, M., Iglesias-Cabeza, N. et al. Early Treatment with Metformin Improves Neurological Outcomes in Lafora Disease. Neurotherapeutics 20, 230–244 (2023). https://doi.org/10.1007/s13311-022-01304-w
NO Ministerio de Economía (España)
NO Fundación Tatiana Pérez de Guzmán el Bueno (España)
NO Instituto de Salud Carlos III (España)
NO National Institute of Neurological Disorders and Stroke of the National Institutes of Health (Estados Unidos)
DS Docta Complutense
RD 14 abr 2025