Lou Gehrig's Disease: Causes and Treatment

“Fans, for the past two weeks you have been reading about the bad break I got. Yet today I consider myself the luckiest man on the face of this earth.”
Lou Gehrig’s farewell speech has been immortalized by baseball fans since his early retirement at the young age of 36. After a record-breaking baseball career, the 1938 season started off with a rapid loss of motor function for Gehrig. His power disappeared, he struggled to run and field routine plays, and every game was a miserable struggle to return to the former prowess he had experienced. Lou was brought to the Mayo Clinic in Chicago for diagnosis of this sudden debilitation. It was discovered that Lou Gehrig suffered from a then obscure disease, Amyotrophic Lateral Sclerosis (ALS), and died only two years after his retirement. His widely publicized bout with ALS has lead to the disease adopting the moniker “Lou Gehrig’s Disease”.
A surefire cause of ALS has yet to be fully discovered. While 10% of ALS cases are hereditary, 90% come from an unknown cause. ALS results from the loss of motor neurons, impairing the ability of the body to send messages to muscles, which results in symptoms like weakening, twitching, difficulty swallowing or breathing, speech problems, and even full-fledged paralysis.
While the cause of ALS seems sporadic, recent discoveries in the field of neuroscience have offered ideas for what may cause this devastating disease when it is not simply inherited. A certain signaling pathway in the brain, the p38 MAPK pathway, may have an effect on the development of ALS. The activation and expression of this particular pathway in motor neurons is positively correlated with the degeneration in mice that have a mutation in the enzyme SOD1.  Inhibiting this p38 pathway can prevent the death of motor neurons induced by the mutated SOD1 enzyme. p38 MAPK signaling increases the amount of nitric oxide (NO) in motor neurons, which can cause oxidative stress. SOD1 mutations can also lead to other cell death pathways in motor neurons, including the activation of the ASK1 cell death pathway.
Yes, there are a lot of esoteric acronyms to remember. But the important take home message is the development of this disease is starting to be understood more fully, even if the initial cause of the mutations in SOD1 and other causes of ALS are relatively unknown.
Although no cure currently exists for ALS, there are multiple treatments. Riluzole (also known as Rilutek) is perhaps the most well-known pharmaceutical treatment, which can help prolong the life of ALS patients. Riluzole acts by blocking certain channels in the brain and preventing a high influx of calcium, which has been known to activate the ASK1 cell death pathway in motor neurons. The decrease in motor neuron death does extend lifespan, however it is not a cure.
ALS still proves to be an unsolved enigma for many scientists. Although headway is being made in the neurological causes and symptoms of ALS, more research must be conducted in the future to find out more about the mechanism of ALS, which will lead to more effective treatments, and hopefully someday, a cure.
 
1) http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001708/
2)https://moodle.cord.edu/file.php/7816/literature/2011/MAPK_review.pdf