But the Hopkins workers found that the machinery that removes the introns from the EAAT2 mRNAs made mistakes in 11 of the 20 sporadic ALS patients they tested. It either failed to remove an unneeded intron, or it deleted an essential protein-coding sequence, called an exon. As a result, the mRNAs make no EAAT2 at all or make a faulty version. Rothstein and his colleagues did not find the abnormalities in brain tissue from 12 normal subjects or in 16 patients who died of other neurodegenerative diseases, including Alzheimer's and Huntington's. This suggests that the EAAT2 defect is specific to ALS and not just a general consequence of nerve cell death.
Many questions remain unanswered.
The researchers do not yet know what causes the mistakes in the mRNAs. It may be that a mutation in the EAAT2 gene gives the cell's RNA-processing machinery the wrong directions for removing the introns. Or the fault may lie in the processing machinery itself. Also unexplained, Rothstein says, is how the defect could be restricted to the motor cortex and spinal cord.