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The Copper Chelator d‐Penicillamine Delays Onset of Disease and Extends Survival in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis
Author(s) -
Hottinger Andreas F.,
Fine Eric G.,
Gurney Mark E.,
Zurn Anne D.,
Aebischer Patrick
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01511.x
Subject(s) - sod1 , amyotrophic lateral sclerosis , penicillamine , transgene , genetically modified mouse , superoxide dismutase , chemistry , in vivo , dismutase , cancer research , disease , gene , biology , medicine , pathology , genetics , oxidative stress , biochemistry
A subpopulation of familial cases of amyotrophic lateral sclerosis has been linked to mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). There is in vitro evidence that certain SOD1 mutants, in addition to their normal dismutation function, show increased ability of the enzyme to act as a peroxidase. This reaction is sensitive to inhibition by copper chelators. To test this hypothesis in vivo , we administered the copper chelator d‐penicillamine to a transgenic mouse model of familial amyotrophic lateral sclerosis overexpressing a mutated form of human SOD1. We demonstrate that oral administration of d‐penicillamine is able to delay the onset of the disease and extend the survival of these mice. Histological studies also showed a decreased loss of facial motor neurons in d‐penicillamine‐treated transgenic mice, corroborating the slower evolution of the disease in these animals. These results suggest that copper chelators may benefit patients with familial amyotrophic lateral sclerosis linked to mutations in the SOD1 gene.