Abstract:

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that causes death of upper and lower motor neurons (MNs) in the central nervous system (CNS). The disease afflicts most people in prime periods of productivity in life, and it is estimated approximately 200,000 individuals in the United States live with ALS and any given time. Though a significant percentage of individuals with ALS have a genetic or hereditary form of the disease, the majority are sporadic cases with unknown etiologies. Regardless of cause, onset and progression of the disease is similar in all ALS patients, with minor initial outward symptoms followed by rapid deterioration of motor function leading to widespread paralysis, respiratory dysfunction and death. Despite the distressing and debilitating nature of ALS, no cures and limited potential treatment options exist. Therefore, identifying targets for effective therapy leading to delayed disease progression, increased quality of life, and extended lifespan are critical areas of investigation. In addition, identifying biomarkers of disease progression is incredibly important as diagnosis often occurs once the disease is in late stages and lifespan is only an average of 3–5 years after diagnosis. As the cellular and physiological processes known to influence or be involved in ALS are numerous, the complexity of the disease is a major detriment in developing effective therapies. Aside from the ubiquitous death of MNs, inflammatory and immunologic response in the spinal cord, brain and target muscles, and signal pathway changes that precede or are induced by MN death have been identified at multiple stages of disease progression. As with most neural disorders and diseases, a multifactorial approach to therapy is likely the most appropriate.