Wednesday, November 19, 2014

ALS Acceleration Linked to Gene Variant

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that results in destruction to the motor neurons of the human body; and thus, loss of proper motor control and functionality. Death of those with this disease commonly occurs due to respiratory failure upon inability to control the muscles that regulate breathing. There are approximately 12,000 Americans that are affected by this disease.

Researchers at the Penn State College of Medicine determined that there existed an association between excess iron accumulation in the brain and ALS. This was aided primarily by the observation that there was a variant of the HFE gene (H63D HFE), linked to iron overload disease, in 30 percent of the ALS patients within their clinic.

The researchers executed a study with mice, intending to determine the effect of carrying the HFE gene variant on the progression of ALS. Mice with the gene variant were crossbred with standard mice typically used for ALS research. Upon examination of the mice, they found that the progression of the disease occurred at a faster rate in those mice that carried the gene variant. For the crossbred mice, lifespan was reduced by 4 percent. These mice also performed more poorly than the normal mice on testing used to evaluate grip strength of the forelimbs and hindlimbs, indicative of reduced control over motor functions. Increased oxidative stress was also noted for those mice with the gene variant, as well as, increased activation of microglial cells. In a neurodegenerative condition like ALS these microglial cells that conventionally aid bodily repair, can actually result in harmful inflammation. Neurofilaments, which transport nutrients through nerve cells, were also found to be more damaged in mice with the gene variant. 


The identification of a gene variant, H63D HFE, in individuals with an accelerated form of the ALS disease has implications to research oriented in treatment for patients. Treatment that may have previously appeared ineffective may actually prove to be efficacious in new studies that differentiate individuals based on whether they have the normal or accelerated form of the disease. Additionally, researchers may be able to focus on determining treatments that will be more effective in populations of patients with the gene variant specifically.

The determination of a link between the H63D HFE gene variant and an accelerated form of the ALS disease is fascinating. A neurodegenerative disease such as ALS that impairs motor function is very debilitating and unfortunate, especially considering the likely death by respiratory failure. This finding may support research in developing differentiated treatments for those with either the normal or accelerated version of the disease, which may prove to be more efficacious. I also found it very interesting that the disease acceleration was so well modeled in the mice. Hopefully this finding aids future ALS research.


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