Lithium delays progression of amyotrophic lateral sclerosis

Francesco Fornai, Patrizia Longone, Luisa Cafaro, Olga Kastsiuchenka, Michela Ferrucci, Maria Laura Manca, Gloria Lazzeri, Alida Spalloni, Natascia Bellio, Paola Lenzi, Nicola Modugno, Gabriele Siciliano, Ciro Isidoro, Luigi Murri, Stefano Ruggieri, Antonio Paparelli

Research output: Contribution to journalArticle

Abstract

ALS is a devastating neurodegenerative disorder with no effective treatment. In the present study, we found that daily doses of lithium, leading to plasma levels ranging from 0.4 to 0.8 mEq/liter, delay disease progression in human patients affected by ALS. None of the patients treated with lithium died during the 15 months of the follow-up, and disease progression was markedly attenuated when compared with age-, disease duration-, and sex-matched control patients treated with riluzole for the same amount of time. In a parallel study on a genetic ALS animal model, the G93A mouse, we found a marked neuroprotection by lithium, which delayed disease onset and duration and augmented the life span. These effects were concomitant with activation of autophagy and an increase in the number of the mitochondria in motor neurons and suppressed reactive astrogliosis. Again, lithium reduced the slow necrosis characterized by mitochondrial vacuolization and increased the number of neurons counted in lamina VII that were severely affected in saline-treated G93A mice. After lithium administration in G93A mice, the number of these neurons was higher even when compared with saline-treated WT. All these mechanisms may contribute to the effects of lithium, and these results offer a promising perspective for the treatment of human patients affected by ALS.

Original languageEnglish
Pages (from-to)2052-2057
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number6
DOIs
Publication statusPublished - Feb 12 2008

Keywords

  • Autophagy
  • Clinical study
  • G93A mice
  • Morphological analysis

ASJC Scopus subject areas

  • Genetics
  • General

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  • Cite this

    Fornai, F., Longone, P., Cafaro, L., Kastsiuchenka, O., Ferrucci, M., Manca, M. L., Lazzeri, G., Spalloni, A., Bellio, N., Lenzi, P., Modugno, N., Siciliano, G., Isidoro, C., Murri, L., Ruggieri, S., & Paparelli, A. (2008). Lithium delays progression of amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 105(6), 2052-2057. https://doi.org/10.1073/pnas.0708022105