Taken from http://www.faqs.org/health/images/uchr_02_img0138.jpg
During the week of December 1st, we talked about amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease. ALS is a neurodegenerative disease that selectively kills off motor neurons travelling from the brain to the spinal cord, causing motor dysfunction, which is typically the first sign that brings patients to a doctor. The disease has a very fast progression with diagnosed patients only having a five year life expectancy after diagnosis. Death from ALS usually results from the inability of a patient to breathe by his/her own accord.
The causes of ALS are relatively unknown and could be the result of genetic predisposition or even purely environmental factors. The pathway leading to motor neuron death, however, has been studied extensively. Overstimulation of excitatory glutamate receptors leads to repeated cell signaling, which is harmful in excess for two reasons. First, near-constant signaling leads to chronic calcium influx into the cell. In other cells, this excess intracellular calcium is not as much of a concern because the cell contains proteins to bind it and also remove it from the cell. The affected motor neurons are unable to keep up with constant stimulation because the cell does not contain enough proteins to bind the excess calcium and maintain balance within the cell. This alone can cause stress to the cellular organelles, especially through the buildup of reactive oxygen species which are a common cause of cellular destruction in neurodegenerative diseases. Second, this repeated stimulation leads to increased protein production, specifically proteins that are secreted from the cell. These proteins are made in an organelle called the endoplasmic reticulum, which normally has a system to check if all protein production is going as planned and to take care of mistakes when they arise. Protein misfolding is liable to occur, especially under increased production demand and oxidative stress. When these misfolded proteins build up to a point where they cannot be removed and degraded, they can inhibit this regulation system causing extreme stress to the endoplasmic reticulum. Once this occurs, the cell will signal for self-destruction.
This intricate pathway has led to many ideas for treatments of ALS. One surprising treat can actually add a few years onto a patient’s life. Doctors advise patients to eat so as to gain as much weight as possible, so long as blood pressure and other vitals are manageable. A cure seems to be far from likely as the causes, as previously stated, are unknown. Links between concussion and ALS were being investigated due to similarities in the degenerative mechanisms of ALS and chronic traumatic encephalopathy (CTE), which is often seen with chronic concussions. Thus far, there have been not been extensive leaps in the path toward a cure. The primary pharmaceutical treatment designed for patients with ALS is a glutamatergic antagonist, which has the potential to cause many adverse side effects due to the widespread glutamate activity in the nervous system. This potential for a variety of side effects holds true for the targeting of many pathways associated with ALS, complicating the issue of treatment development. It is very unfortunate to see a disease be nearly unstoppable once onset begins. Personally, I believe more research should be done on early detection of ALS as well as treatments aimed at more effectively halting progression, while avoiding side effects. In the case of a disease like this with such a low life expectancy, all fronts must be addressed so as to provide the best care possible to patients.
