Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder 
characterized by motoneuron degeneration, resulting in muscle paralysis and 
death, typically within 1-5 years of diagnosis. Although the pathogenesis of ALS 
remains unclear, there is evidence for the involvement of proteasome dysfunction 
and heat shock proteins in the disease. We have previously shown that treatment 
with a co-inducer of the heat shock response called arimoclomol is effective in 
the SOD(G93A) mouse model of ALS, delaying disease progression and extending the 
lifespan of SOD(G93A) mice (Kieran et al. 2004). However, this previous study 
only examined the effects arimoclomol when treatment was initiated in pre- or 
early symptomatic stages of the disease. Clearly, to be of benefit to the 
majority of ALS patients, any therapy must be effective after symptom onset. In 
order to establish whether post-symptomatic treatment with arimoclomol is 
effective, in this study we carried out a systematic assessment of different 
treatment regimes in SOD(G93A) mice. Treatment with arimoclomol from early (75 
days) or late (90 days) symptomatic stages significantly improved muscle 
function. Treatment from 75 days also significantly increased the lifespan of 
SOD(G93A) mice, although treatment from 90 days has no significant effect on 
lifespan. The mechanism of action of arimoclomol involves potentiation of the 
heat shock response, and treatment with arimoclomol increased Hsp70 expression. 
Interestingly, this up-regulation in Hsp70 was accompanied by a decrease in the 
number of ubiquitin-positive aggregates in the spinal cord of treated SOD(G93A) 
mice, suggesting that arimoclomol directly effects protein aggregation and 
degradation.