Problem Occurs In 65 Percent Of Spontaneous ALS Patients

Johns Hopkins researchers have identified genetic mutations that appear to cause or contribute to more than half of all non-inherited or sporadic cases of the deadly muscle disease amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease.

"If these mutations really are specific to ALS and we can develop a test to detect them, that could help us make the diagnosis and begin treatment much earlier in the course of the disease," says Jeffrey Rothstein, M.D., Ph.D., associate professor of neurology.

The newly identified mutations involve a protein called EAAT2, which normally deactivates and recycles glutamate, a chemical certain nerve cells use to send messages to each other.

Hopkins researchers had previously shown that many ALS patients have little or no EAAT2 in certain areas of the brain and spinal cord, creating an excess of glutamate that kills the nerves that control muscles.

This usually leads to paralysis and death in two to five years. Nearly 30,000 people currently have the disease, and 95 percent of them are thought to have the sporadic form.

The Hopkins team first found evidence of the mutation in a patient who had the inherited form of ALS and unusually reduced levels of EAAT2. The problem, the researchers discovered, was an error in the way the patient's nerve cells were translating the DNA code for EAAT2 into RNA.

Cells use RNA as the blueprint for building a protein. As they translate DNA into RNA, they normally cut out useless bits of DNA called introns and paste together the active parts, called exons. If the introns are not properly removed, they disrupt the blueprint and prevent the cell from making the protein properly.

"In this patient," Rothstein explains, "there were problems in the cutting and pasting
'"/>

Contact: Michael Purdy
mpurdy@welchlink.welch.jhu.edu
(410)955-8725
Johns Hopkins Medical Institutions
21-Mar-1998