The True ALS Challenge

The ALS Ice Bucket Challenge has flooded social media outlets in the last few months and created a buzz around this neurodegenerative disease. It has jumped to the forefront of charitable causes, overshadowing many big organizations like the American Cancer Society.
But how much do people really know about ALS? I have watched dozens of videos of friends who have dowsed themselves in frigid water and pledged to donate to the ALS foundation to contribute to the cause. However, if anyone asked me what ‘ALS’ stood for or the effects of the disease two weeks ago, I wouldn’t be able to answer. I had no idea that about 15 people are diagnosed every day with Amyotrophic Lateral Sclerosis. I also learned that ALS, commonly known as Lou Gehrig’s Disease, mainly affects Caucasian males between the ages of 40 and 70.[1] Also, the majority of cases occur because of sporadic gene mutations. The next diagnosis could easily be a parent, a professor, a coworker, or a neighbor.
This great act of charity has raised a lot of money quickly, but where is that money going? The true results of these awareness campaigns lie in research trials that eventually lead to potential drug treatments. ALS is a frightening disease that decreases muscle function until the lungs and heart stop functioning. All the while, the person maintains their cognitive abilities. Research focuses on finding ways to decrease the extent and rate of motor function loss associated with the disease.
The one drug treatment available for ALS, Riluzole, is an antiglutamatergic drug. It acts by inhibiting the voltage-gated ion channel NMDA and reduces release of the neurotransmitter glutamate. As promising as this is, the exact mechanism of action is unknown. In the review article, the role of the glutamate acting on the NMDA receptor is discussed in detail. The grounds for this research are founded by evidence of high levels of glutamate in the plasma and cerebral spinal fluid of ALS patients as well as the toxic role NMDA plays in leading to cell death. The research focuses on glutamate’s excitatory actions in the spinal cord.

NMDA activation: https://www.youtube.com/watch?v=Q_z5ZL9STMw  
Overexcitation of a cell by glutamate may lead to a number of pathways that lead to the same end result, cell death. One mechanism involves the endoplasmic reticulum (ER), the organelle responsible for modifying proteins into their functional form. Overactive NMDA receptors increase ER stress which depletes Ca2+ stores. Without proper balance of this ions ER cannot function properly which leads to improper folding of important proteins. This may have a connection to a common mutation in ALS patients found on the SOD-1 protein where it is not folded into its functional form.
Cell death from increased Ca2+ levels is more likely to occur when it is transported by over-active NMDA receptors than other receptor types. A similar toxic effect to ER stress is found in the mitochondria which produces reactive oxidative species during the oxidative production of ATP. These, along with numerous other pathways, link glutamate to the physiological effects of ALS. Because the only drug for ALS targets the glutamate-NMDA interaction and the contribution of NMDA in cell destruction, there is no denying its implications for possible drug treatments for the disease.
The real task is not completing the ALS Ice Bucket Challenge within 24 hours. It’s planting the seed of interest to the general public and pursuing that with ample research. If we use the Ice Bucket Challenge as a platform for discussion on this topic, then a wider audience may be reached and informed about this disease. I have discussed one area that is currently being examined for therapeutic purposes for ALS.  I would like people to step away from the camera, and begin to dig deeper into the topic. To question where research is headed for ALS treatment. Without the ALS Ice Bucket Challenge as an attention grabber, I may not have had the opportunity to learn as much as I did and to share the most recent research. Continue to stay informed on the direction of research and keep on the lookout for the positive outcome of the ALS campaign in the future.


[1] http://www.alsa.org/about-als/who-gets-als.html
Link to article mentioned: http://www.sciencedirect.com/science/article/pii/S0925443912002736

1 Comment

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