Mice bred to carry a gene variant found in a third of ALS patients have a faster disease progression and die sooner than mice with the standard genetic model of the disease, according to Penn State College of Medicine researchers. Understanding the molecular pathway of this accelerated model could lead to more successful drug trials for all ALS patients. Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a degeneration of lower and upper motor neurons in the brainstem, spinal cord, and the motor cortex. The disease, which affects 12,000 Americans, leads to loss of muscle control. People with ALS typically die of respiratory failure when the muscles that control breathing fail. Penn State researchers were the first to discover increased iron levels in the brains of some patients with the late-onset neurodegenerative disorders Parkinson's disease and Alzheimer's disease. A decade ago, they also identified a relationship between ALS and excess iron accumulation when they found that 30 percent of ALS patients in their clinic carried a variant of a gene known as HFE [high iron (Fe)] that is associated with iron overload. For this study, the researchers crossbred mice with the H63D HFE gene variant with the standard mice used in ALS research. "When we followed the disease progression and the behavior of our crossbred mice compared to the standard mice, we saw significant differences," said Dr. James Connor, vice chair of neurosurgery research and director of the Center for Aging and Neurodegenerative Diseases. The crossbred mice performed significantly worse on tests of forelimb and hindlimb grip strength and had a 4 percent shorter life span. The researchers published their findings in the December 2014 issue of the BBA Molecular Basis of Disease.
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