Research validates five new genes responsible for ALS

An article on Science Daily states the study Dr. Robert Bowser conducted at St. Joseph's Hospital and Medical Center.  The experiment found a link between genes and Amyotrophic Lateral Sclerosis. ALS is a fatal disease that progresses over time affecting the motor neurons and ultimately muscle control. A new technology, IBM Watson for Drug Discovery, was used that provided evidence that RNA metabolism has an effect on the development of ALS. It was found that 11 out of the 30 genes linked to ALS were mutated and caused different forms of ALS. These mutations alter RNA metabolism which affect the motor neurons, leading to a loss in muscle control/movement and paralysis. There are 1,500 RNA binding proteins so it is plausible other genes contribute to ALS. With IBM Watson for Drug Discovery, those genes will be tested for and that information will be able to be obtained faster.

I believe the advancement of technology will change medicine. ALS is a horrible disease, with no known cure. Finding five genes that contribute to the disease will be helpful in understand the disease better and coming up with an effective treatment. As technology improves, more genes will be tested and identified. This is just the beginning and the future of medicine seems to be brighter.

https://www.sciencedaily.com/releases/2017/12/171201104101.htm
https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis

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

Deep Brain Stimulation May Unlock the Cure to Tourette’s Syndrome

Tourette’s syndrome is a neurological disorder that causes individuals to make involuntary movements and loud noises. There is currently no cure for Tourette’s syndrome; however, specialists at the University of Florida's Center for Movement Disorders are looking to change that. Specialties at the center are performing experimental surgery in Tourette’s patients.  The procedure, deepbrain stimulation (DBS), is currently used in patients with movement disorders such as Parkinson's disease or tremors.

Deep brain stimulation is based off the delivery of electricity and works by implanting small electrodes into the brain in order to stimulate affected regions in patients with movement disorders. The electrodes are attached to an impulse generator and the generator, which is also referred to as a pacemaker, provides electrical impulses to the affected regions of the patient’s brain. The connections between neurons are affected by the impulses which stop the abnormal activity that the patients are presenting with.

While DBS has been performed in over 100,000 patients since 1997 it has never been performed in Tourette’s patients. The underlying neurology in Tourette’s patients is different from that of other conditions treated with DBS because it combines both emotion and motor activity. Specifically, in Tourette’s patients the movement is not there all the time; the patients have a buildup, tic, and an urge and until they can move the patients do not feel better. The only current available treatments for Tourette’s syndrome are behavioral therapy and drug medications; however, these treatments only alleviate the severity of the tic they do not prevent the tics all together.

In September 2014 DBS was performed in a patient with Tourette’s syndrome for the first time. Additionally, the patient had a new grid-like device implanted on top of her brain. This device is intended to gather information from the patient’s brain that can hopefully lessen her tics, and possibly someday stop them. Over the next six to twelve months the patient’s brain activity will be monitored with the grid providing key insights into the underlying cause of her Tourette's syndrome. Understanding the underlying causes of the syndrome will allow doctors to regulate the electrical impulses to in order to manage and hopefully eliminate the tics all together.

This article really caught my attention me because I am very interested in neurological disorders and learning more about them. Tourette’s syndrome is an interesting and difficult disorder because of both the physical and emotional combination. It will be interesting to see over the next several months how well DBS works in this patient. I am hopeful that this procedure will be the next step in learning not only more about the disorder but will be able to eliminate the symptoms experienced by Tourette’s patients.  

Main Article: http://www.cnn.com/2014/10/27/health/deep-brain-stimulation-tourettes/index.html?hpt=he_bn3

Secondary Article: http://tsa-usa.org/dbs/DBSfall09x.html

Genetic Cause Discovered for Rare Disorder of Motor Neurons

Scientists have finally discovered the genetic cause for a rare disorder of motor neurons, and believe this may help find causes of similar  diseases.  There are many neuromuscular disorders which are caused by disorders in the motor neurons that ultimately damage the nervous system, and can weaken and destroy muscle.  Unfortunately most of these disorders do not have a cure.  The study led by  Professor Andrew Crosby and Dr Meriel McEntagart at St George's, University of London, has discovered the gene mutation that causes a rare disorder of motor neurons called distal hereditary motor neuropathy (dHMN).   dHMN typically affects muscles of the hands and feet, and can causes a hoarse voice. Symptoms usually begin during childhood, but can still appear up to the mid 30s. They used a family of 26 members, all of which carried the mutation but only 14 actually had the disease.   They found that mutation of the gene (SLC5A7)  disrupts the function of a molecule called the choline transporter (CHT). CHT is carries an essential nutrient called choline to the neuromuscular junctions. This disruption to the function of the neuromuscular junctions leads to the debilitating symptoms, and causes dHMN.



The researchers say their findings raise a possibility that mutations of the same gene or genes with similar roles might underlie other disorders involving motor neurons. This will not only open up treatment options for people suffering from dHMN but also potentially for many other terrible diseases relating to the nervous system and motor neurons.