Imagine this:
You are a 45 year old individual. You are married and have school-aged kids. You have a successful career in which you have found fulfillment. Overall, you’re a pretty healthy individual. Generally, you are happy. However, you’ve recently been experiencing muscle weakness and the occasional muscle spasm. After a couple of weeks you finally decide to get it checked out. With a few tests, the doctor calls to give you the news: you have been diagnosed with amyotrophic lateral sclerosis (ALS) with a prognosis of 3-5 years. In a moment your life has become infinitely more complicated. You must consider how to manage this disease as well as what steps you will need to take to provide for your family after you are gone.
While this may seem dramatized, it is likely all too true for many individuals suffering from ALS. ALS is a neurodegenerative disease that is characterized by the progressive loss of motor neurons. This disease is popularly known as Lou Gehrig’s disease. Approximately 20,000-30,000 individuals in the United States have ALS with 5,000 being diagnosed annually. The disease typically has a fast progression with a mean survival time of 3-5 years. Symptoms progress from localized muscle weakness, fatigue, slurred words, poor balance and a weak muscle group to the loss of function of most voluntary muscles, requiring assistance in breathing and the use of a feeding tube. There is currently little to be done to treat ALS. When patients are diagnosed they are encouraged to gain a reasonable amount of weight as fat reserves will be able to provide energy as the disease progresses. Currently, riluzole is the only pharmaceutical approved for the treatment of ALS. It works by decreasing calcium influx and indirectly blocks the stimulation of glutamate receptors. It has been shown to extend the life expectancy by 3-5 months and delays the need for a tracheostomy or ventilator dependence. With few treatment options, care for ALS patients is primarily aimed at providing comfort and independence.
Although we do not yet understand the mechanism behind ALS, we do know that disturbances in calcium homeostasis and protein folding are essential features of neurodegeneration. Because of this, folding proteins are a hopeful target for pharmacological treatment of ALS. The ultimate goal is to stabilize the folding of proteins and prevent their aggregation. Currently, there are two ways in which scientists hope to modulate ER stress that leads to improper folding of proteins. One approach aims to inhibit the ER stress pathway, ultimately preventing cell death. The second method aims to induce the unfolded protein response with the hope that proteins will be able to be properly folded. Although these methods work in two very different ways, both hope to correct noted problems associated with ALS. Our lack of knowledge on the pathology of ALS highlights the need for research on this disease. With a better understanding of the disease there is hope to provide better care to those who suffer from it.
ALS: A Tough Disease to Swallow
