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Efficient three‐drug cocktail for disease induced by mutant superoxide dismutase
Author(s) -
Kriz Jasna,
Gowing Geneviève,
Julien JeanPierre
Publication year - 2003
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10500
Subject(s) - riluzole , amyotrophic lateral sclerosis , sod1 , gliosis , pharmacology , minocycline , medicine , neurodegeneration , glutamate receptor , neuroprotection , disease , biology , pathology , receptor , antibiotics , biochemistry
There is currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS). Because evidence suggests that multiple pathways may contribute to ALS pathogenesis, we tested in a mouse model of ALS (SOD1 G37R mice) a combination approach consisting of three drugs for distinct targets in the complex pathway to neuronal death: minocycline, an antimicrobial agent that inhibits microglial activation, riluzole, a glutamate antagonist, and nimodipine, a voltage‐gated calcium channel blocker. The efficacy of this three‐drug cocktail was remarkable when administered in the diet from late presymptomatic stage (8–9 months). It delayed the onset of disease, slowed the loss of muscle strength, and increased the average longevity of SOD1 G37R mice by 6 weeks. The protective effect of the treatment was corroborated by the reduced immunodetection signals for markers of gliosis and neurodegeneration in the spinal cord of SOD1 G37R mice. These results indicate that such three‐drug combination may represent an effective strategy for ALS treatment. Ann Neurol 2003