Motor Neuron Disease (MND) is an illness in which the nerve cells that carry signals from the brain to the muscles gradually deteriorate. Researchers at the University of Michigan have made progress in understanding this devastating illness which may pave the way for better diagnosis and research on treatments.
They have found mutations in one key gene (neuropathy target esterase, or NTE) that cause a previously unknown type of inherited motor neuron disease.
Interestingly, the researchers found that the mutations caused changes in a protein already known to be involved when people develop neurologic disorders as a result of exposure to toxic organophosphates—chemicals commonly used in solvents and insecticides and also as 'nerve gas' agents.
According to researchers, this discovery points to a new lead in the search to understand MND.
"We speculate there may be gene-environment interactions that cause some forms of motor neuron disease," said John K. Fink, M.D., professor of neurology at the U-M Medical School and senior author of the new study.
"Our findings support the possibility that toxic organophosphates contribute to motor neuron disease in genetically vulnerable people," he added.
He believes the results suggest that altered activity of the gene found in patients in the study may also contribute to other motor neuron disorders, possibly including Lou Gehrig's disease or ALS (amyotrophic lateral sclerosis).
Scientists have not yet understood the exact manner in which toxic organophosphate exposure causes progressive and permanent nerve damage, but they have learned that this process involves disturbance of an enzyme, NTE, contained within nerves.
For the study, Fink examined members of two families who had progressive weakness and spasticity in their legs, as well as muscle atrophy in their hands, shins and feet.
The researchers not only studied nerve and motor function but also performed genetic studies and determined that the gene for the condition was on a region of chromosome 19.
They performed genetic analysis that confirmed this location and excluded other areas in the genome.
Among the many genes in this region of chromosome 19, one gene stood out as particularly likely: the gene that encodes for NTE.
Because of its known role in organophosphate-induced neurological disease, the NTE gene was considered an important candidate gene and was studied immediately.
After the analysis, the researchers found that the affected people in each family had NTE gene mutations. These mutations altered a critical part of the NTE protein called the esterase domain.
The study appears in the March issue of the American Journal of Human Genetics.