Spinal and bulbar muscular atrophy, also known as Kennedy's disease, is an 
adult-onset hereditary neurodegenerative disorder caused by an expansion of the 
polyglutamine repeat in the first exon in the androgen receptor gene. 
Pathologically, the disease is defined by selective loss of spinal and bulbar 
motor neurons causing bulbar, facial and limb weakness. Although the precise 
disease pathophysiology is largely unknown, it appears to be related to abnormal 
accumulation of the pathogenic androgen receptor protein within the nucleus, 
leading to disruption of cellular processes. Using a mouse model of spinal and 
bulbar muscular atrophy that exhibits many of the characteristic features of the 
human disease, in vivo physiological assessment of muscle function revealed that 
mice with the pathogenic expansion of the androgen receptor develop a motor 
deficit characterized by a reduction in muscle force, abnormal muscle 
contractile characteristics, loss of functional motor units and motor neuron 
degeneration. We have previously shown that treatment with arimoclomol, a 
co-inducer of the heat shock stress response, delays disease progression in the 
mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis, a 
fatal motor neuron disease. We therefore evaluated the therapeutic potential of 
arimoclomol in mice with spinal and bulbar muscular atrophy. Arimoclomol was 
administered orally, in drinking water, from symptom onset and the effects 
established at 18 months of age, a late stage of disease. Arimoclomol 
significantly improved hindlimb muscle force and contractile characteristics, 
rescued motor units and, importantly, improved motor neuron survival and 
upregulated the expression of the vascular endothelial growth factor which 
possess neurotrophic activity. These results provide evidence that upregulation 
of the heat shock response by treatment with arimoclomol may have therapeutic 
potential in the treatment of spinal and bulbar muscular atrophy and may also be 
a possible approach for the treatment of other neurodegenerative diseases.