Johns Hopkins scientists believe they have moved a crucial step closer to explaining what causes Lou Gehrig's disease, finding that victims lack a protein needed to prevent the death of nerve cells in the brain and spinal cord.
While the researchers do not claim to have cracked all elements of the mystery, they say their finding may supply the direction needed to fashion drugs capable of slowing or arresting the disease's fatal course.
Technically known as amyotrophic lateral sclerosis, or ALS, the disease destroys cells that are responsible for relaying messages to muscles throughout the body. Death usually comes within two to four years when victims can no longer breathe.
"I can't tell you this is the absolute answer to ALS, but this may be a component of what causes the disease," said Dr. Jeffrey D. Rothstein, the Hopkins neurologist who reports his findings in today's New England Journal of Medicine.
"We think that if we could stop this defect, we might slow the disease or, in the extreme, arrest it."
The disease got its popular name from the famed hitter on the New York Yankees baseball team whose life it claimed in 1941.
Most victims first experience weakness in the arms and legs, but ultimately are helpless to move, speak or swallow. The disease is particularly wrenching because victims retain their ability to think and perceive their surroundings while they slowly die.
It afflicts 20,000 to 30,000 people in the United States, killing 5,000 each year.
The Hopkins team built upon previous knowledge of glutamate, one of the many chemicals that communicate messages from one cell to another along the neural pathways of the brain and spinal cord. Among its functions, glutamate relays messages between the specialized nerve cells called motor neurons, which control movement.
For two decades, scientists have known that excess amounts of glutamate can destroy neurons. And in 1990, researchers at Hopkins learned that ALS patients had elevated levels of the chemical.
In the most recent finding, Dr. Rothstein and his colleagues found that ALS victims lacked a protein that regulates the amount of glutamate that bathes the motor neurons. The protein suctions the chemical off the surface of motor neurons an instant after the message has been conveyed.
The result is "too much of a good thing," a killing flood of glutamate instead of a healthy trickle, said Dr. Rothstein.
Scientists noticed the defect when they compared people who had died of Lou Gehrig's disease with patients who had Alzheimer's and Huntington's -- two other degenerative nerve diseases -- and still others who did not have a neurologic illness.
Autopsies showed that only the ALS patients lacked the essential protein.
Cautioning that a cure is still a long way off, Dr. Rothstein said the next step could be drugs to block glutamate from attaching to the motor neurons. Such drugs, in effect, would erect a floodgate.
A Hopkins team is already experimenting with drugs that block glutamate in laboratory cultures of spinal cells from rats. Once researchers find out which drugs are best, a further step would be to try the drugs in human subjects.
The goal would be to slow the destruction of motor neurons that are still healthy, or to arrest the destruction altogether, according to Dr. Rothstein.
Unfortunately, science has yet to come up with a way to revive nerve cells once they have died, so the drugs would not enable ALS patients to regain motor functions they have lost.
Dr. Marinos Dalakas, chief of the neuromuscular disease section at the National Institute of Neurological Disorders and Stroke, called the Hopkins research "an important study that has been very carefully done." But he said it has yet to be proved that poor regulation of glutamate is the cause -- not the result -- of cell death.
If further studies prove that it is the cause, he said, glutamate-blocking drugs may provide new hope for an effective treatment.