Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition in which motoneurons of the spinal cord and motor cortex die, resulting in progressive paralysis1,2. This condition has no cure3 and results in eventual death, usually within 1–5 years of diagnosis1,2. Although the specific etiology of ALS is unknown, 20% of familial cases of the disease carry mutations in the gene encoding Cu/Zn superoxide dismutase-1 (SOD1)4. Transgenic mice overexpressing human mutant SOD1 have a phenotype and pathology that are very similar to that seen in human ALS patients5,6. Here we show that treatment with arimoclomol, a coinducer of heat shock proteins (HSPs), significantly delays disease progression in mice expressing a SOD1 mutant in which glycine is substituted with alanine at position 93 (SOD1G93A). Arimoclomol-treated SOD1G93A mice show marked improvement in hind limb muscle function and motoneuron survival in the later stages of the disease, resulting in a 22% increase in lifespan. Pharmacological activation of the heat shock response may therefore be a successful therapeutic approach to treating ALS, and possibly other neurodegenerative diseases.
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We thank Biorex R&D (Hungary) for the gift of arimoclomal. L.G. is the Graham Watts Senior Research Fellow funded by the Brain Research Trust. D.K. is in receipt of a Brain Research Trust Prize Studentship.
As a consequence of the work presented in this paper, G.B. and L.G. are named on a patent application by Biorex R & D Co., Hungary.
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Kieran, D., Kalmar, B., Dick, J. et al. Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat Med 10, 402–405 (2004). https://doi.org/10.1038/nm1021
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