WASHINGTON, DC - Scientists have discovered two mutations that can be major contributors to the development of the lateral sclerosis amyotrophic (ALS), or Lou Gehrig's disease. The discovery, presented here today at the annual meeting of the Society for Neuroscience, may one day lead to a useful diagnostic test and improved treatments.
ALS, which affects around 30,000 people worldwide, causes progressive paralysis which usually results in death. Although scientists have discovered a gene that causes an inherited form of the disease in 1993, the majority of cases - over 0% - are "sporadic", which is not hereditary, and are due to unknown causes
. Jeffrey Rothstein, a neurologist at Johns Hopkins University, found mutations in 10 of 20 patients with sporadic ALS. It was followed earlier observations that many patients have abnormally low levels of EAAT2, a protein that helps turn off and recycling the neurotransmitter glutamate in the brain and spinal cord. Due to excessive glutamate concentrations are toxic to neurons, suggesting paralysis patients could be caused by accumulation of the neurotransmitter and the resulting death of neurons that control muscles.
In the current work, the Hopkins team found a possible explanation for the deficiency EAAT2 in ALS: the mutations they identified are nucleic acids that translate the genetic code into the structure protein. He and his colleagues did not find mutations in healthy subjects or in patients with Alzheimer's disease or Huntington's disease, which are also characterized by the death of neurons.
The work is preliminary, Rothstein said, and he recognizes it leaves many questions unanswered. For example, researchers have found that the modified proteins in the cells of the brain controlling motor function; they can not explain why the changes are limited to those cells. And many experts are not convinced that the metabolism of faulty glutamate is the main culprit in the disease. Rothstein said, however, that the only drug that has shown promise against ALS is Rilutek, which inhibits glutamate production. Although protein mutations do not play a major role in the disease, he said, they could help neurobiologists track down the actual cause.
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