Motor neurone disease, or amyotrophic lateral sclerosis, is a serious 
progressive neurological disorder, characterized by loss of UMN and LMN. 
Pathological features include characteristic intracytoplasmic MN inclusion 
bodies and appearances on ubiquitin staining. The aetiopathogenesis of the 
disease remains unknown and there is, to date, no effective treatment. Several 
abnormalities have been demonstrated in neurotransmitter, neuropeptide and gene 
expression studies. Abnormalities in glutamate metabolism have led to the 
excitotoxin hypothesis of MN destruction. Other theories include deficits in MN 
trophic factors, trans-synaptic degeneration, impaired ability to detoxify 
putative toxic agents and impaired DNA/RNA metabolism. The existence of familial 
forms, some of which show linkage to markers in chromosome 21, allows a genetic 
approach to the mechanisms of disease. Recent studies suggest that mutations in 
the Cu/Zn SOD gene may be important in some of the familial forms. The atypical 
forms seen in the Western Pacific have stimulated a search for environmental 
agents. Agents undergoing therapeutic trials at present include CNTF, IGF1 
glutamate antagonists, branched-chain amino acids and TRH analogue.