Lithium delays progression of amyotrophic lateral sclerosis.
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.
Fornai
Francesco
F
Department of Human Morphology and Applied Biology, University of Pisa 56100 Pisa, Italy. f.fornai@med.unipi.it
Longone
Patrizia
P
Cafaro
Luisa
L
Kastsiuchenka
Olga
O
Ferrucci
Michela
M
Manca
Maria Laura
ML
Lazzeri
Gloria
G
Spalloni
Alida
A
Bellio
Natascia
N
Lenzi
Paola
P
Modugno
Nicola
N
Siciliano
Gabriele
G
Isidoro
Ciro
C
Murri
Luigi
L
Ruggieri
Stefano
S
Paparelli
Antonio
A
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects
D018020:Lithium Compounds