NEW YORK (Reuters Health) - A mutation in a gene that codes for a protein responsible for moving materials around nerve cells can trigger muscle weakness and wasting in an inherited muscle disease, new research suggests.

The study involved people with a rare inherited muscle disease, but the identification of the mutation may lead to a better understanding of other motor neuron diseases, including amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.

Motor neurons are nerve cells along which the brain communicates with muscles. When motor neurons are damaged, muscles may gradually weaken until they no longer work at all.

In the study, a team led by Dr. Imke Puls of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, examined the genes of a family with an inherited motor neuron disease. The first symptoms of the illness, which begin in early adulthood, include breathing difficulty, worsening facial weakness and wasting in the hands. As the disease gets worse, muscle wasting spreads to the feet and legs.

The researchers found that family members with the disease had a mutation in a gene that contains the instructions for a component of a protein called dynactin. Dynactin is essential for transporting nutrients and other substances within nerve cells. Normally, it makes sure that nutrients move properly down "tracks" called microtubules in nerve cells.

But in the family with the motor neuron disease, the mutation reduces the ability of dynactin to guide nutrients on these tracks. Dynactin's function is not completely wiped out, though, which may explain why this particular type of motor neuron disease is relatively mild and does not start until adulthood, the researchers suggest.

Puls and her colleagues suspect that a mutation that causes more severe interference with dynactin may result in more serious disease.

Results of the research are published in the advance online edition of the journal Nature Genetics.

"We found that a mutation in a protein involved in transport is causing the disease," Puls told Reuters Health. Scientists have suspected that transport problems are involved in motor neuron diseases, but this is the first proof in human disease, according to Puls.

This discovery may encourage other researchers to investigate transport problems, which could lead to improvements in diagnosis and treatment, Puls said. But the researchers cautioned that diagnostic and therapeutic advances "will definitely take more time."

The next step, Puls said, is "to find out why this particular mutation leads to a motor neuron disease since the protein is expressed in each single cell of the body but only motor neurons become sick."

SOURCE: Nature Genetics 2003;10.1038/ng1123.