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.

Link to Article: http://www.medicalnewstoday.com/releases/285478.php

Related Links:

http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_als.htm

http://www.pnas.org/content/100/26/15788.full

Genotype found in 30% of ALS Patients Speeds up Disease Progression

Penn State College of Medicine researchers have recently discovered that there is a gene variant that is found in 1/3 of ALS patients which leads to a faster disease progression. Amyotrophic lateral disease, ALS is a degenerative disease in the brain, spinal cord and motor cortex. These researchers also discovered that there is a relationship between ALS and an excess of iron. They discovered this when they found that 1/3 of ALS patients contained a gene variant of HFE which is associated with iron overload. 

The experiment consisted of comparing regular mice used in ALS research with crossbred mice containing the HFE gene variant. There were major differences between the two groups when it came to the tests of the forelimbs and hindlimb grip strength. The crossbred mice did significantly worse on this compared to the regular mice and their life span was four percent shorter. This proved that when the HFE gene is present the disease got worse more quickly. 

The lead researcher of this experiment found that the HFE gene variant caused the disease to sped up more quickly in the female mice cause them to die quicker than the male. This was fairly interesting because on average males with ALS die faster than females with ALS. The crossbred mice also showed more oxidative stress and microglial activation and these cells usually help repair the body but an excess of them can cause harm. 

The conclusion is that when the HFE gene variant is present it makes matters much worse. This conclusion can lead to more treatments. Separating patients who have ALS with the HFE gene variants from patients who have just ALS can lead to treatments and medicines that can treat each one separately and benefit everyone.

Main Article:http://www.sciencedaily.com/releases/2014/11/141113085114.htm

A Certain Gene Increases the Progression of ALS

        Amoytrophic lateral sclerosis is a disease that involves the degeneration of the lower and upper motor neurons of the brainstem, resulting in those with the disease to loss of muscle control and ultimately death. One third of ALS patients are believed to have a gene that causes a faster progression of the disease. When mice were given this genetic variant, the disease progressed faster and the mice died sooner than the mice that did not have the genetic variant.
       
        About 10 years ago, researchers at Penn State found a link between the amount of iron accumulation in the brain in patients with nuerodegenerative disorders (Parkinson's and Alzheimer's disease). These researchers also found that about of third of their ALS patients had an accumulation of iron and had a genetic variant, HFE, that is associated with iron overdose diseases. In order to test the relationship between iron accumulation and the HFE variant, researchers crossbred mice with the HFE gene and standard mice.

This picture shows the difference between normal nerves and how the nerve fibers start to deteriorate and muscles weaken in those who have ALS.

        When studying the mice, James Connor, vice chair of neurosurgery research and director for the Center for Aging and Neurodegenerative Diseases, and his team found that the crossbred mice performed worse on test for hind limb and forelimb strength and had a 4% shorter life span. Their observations led them to conclude that when a mouse with the HFE variant was infected with ALS, the disease progressed much more rapidly than in the mice that did not have the variant. The grad student that was running the study, Wint Nandar, also realized that the females' disease progression was much faster in females with the variant than in males; however, normally, males with the disease would die faster than females.
 
        The researchers also found that the infected mice showed a greater degree of oxidative stress and microglial activation. Microglial cells are normally responsible for repairing the body, but when they are over-activated, they can cause inflammation, a factor that does not help with the progression of the disease. The mice with the genetic variant were also seen to have a disruption of the nuerofilaments, fibers that transport nutrients through the nerve cells, another reason why the disease can progress faster when HFE is present.

          I think that this a very important study that can be very valuable to those that are trying to find a cure for ALS, or some type of treatment. Knowing the genetic background an individuals can help researchers determine why some of their products work for some patients and not others. ALS is a very detrimental disease and anything that is going to hep researchers get a better understanding of the disease would be extremely beneficial.

Original Article: Genotype found in 30 percent of ALS patients speeds up disease progression