The Science of ALS, Harvard Research, and The Ice-Bucket Challenge

by / 0 Comments / 315 View / August 19, 2014

I peered into the icebox at the local grocery store at 9:30 on a Wednesday morning and found it empty. However, just as I was about to walk away dejected, I spied a lone bag of ice hiding in the corner. I quickly grabbed it, ran to the register, and then sped to my friend’s house. The reason for my mad ice hunt? The ice bucket challenge. Although I usually try my hardest to lurk in the shadows of trends like plunging into a frigid lake to escape donating a hundred dollars and other flamboyant displays of altruism, this was different. Ever since one of my relatives was recently diagnosed with a neurodegenerative disease, I felt a lack of awareness of the causes, symptoms, and treatments of these types of conditions. This lack of public awareness leads to a smaller portion of intelligent college students pursuing research in such fields, leaving patients with these lesser known diseases with no hope of rapid progress. Therefore, I am glad that this trend, either directly or indirectly, benefits patients living with a specific and small-scale disease, ALS.

Amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig’s disease, is a neurodegenerative disease affecting nerves in the frontal lobe of the brain and the spinal cord. The nerves affected, called motor neurons, control voluntary muscle movement and extend into the muscle tissue. As the motor neurons begin to die, the brain has increased difficulty in the initiation and control of the muscles. Of course, this only refers to the muscle movements that require initiation and termination through the brain. In other words, voluntary muscle movement. Thus, the heart, digestive system, and other involuntary mechanisms throughout the human body are not affected by this disease. However, since breathing is a voluntary action, patients with ALS can experience problems with their circulatory system. As shown by Stephen Hawking, possibly the most famous ALS patient, although the disease can lead to paralysis, the life expectancy is highly variable. Despite Hawking’s diagnosis in his teens and complete loss of muscle movement shortly after, he outlived the 2-5 year death mark by over 50 years.

Despite the progress researchers have made, several unknown factors remain. The cause itself, for example, is largely unknown: 5-10% of ALS patients have a family history of the disease, inheriting several mutated genes, while 90-95% acquire the disease through environmental factors. Around 33% have a defect in the gene Crorf72 and 20% in the gene coding for the SOD1 enzyme. However, researchers are still unsure about the mutation’s link to the physical manifestation of ALS. Several possibilities exist, ranging from defects in structure of motor neurons to an increased vulnerability to environmental factors, specifically toxins.

Kevin Eggan, a researcher at Harvard Stem Cell Institute, recently published a paper hinting at both the cause and possible drug treatment of ALS. In 2007, his team found in the mouse model that glial cells, a specific component of the central nervous system, played a role in the motor neuron degeneration in certain forms of ALS. One year later, prostanoid molecules, known to take part in the inflammation process, were identified as a factor in the function of glial cells, and, in ALS patients, the dysfunction. With this knowledge, the team began to search for a drug to inhibit the overexpression of prostanoid receptors in these patients. They then genetically manipulated mice to possess mutations, characteristic of those with ALS, and placed their cells with normal human motor nerve cells, derived from stem cells. Soon, it became clear that regular doses of the inhibitory drug reduced damage to the muscle tissue and motor neurons. Taking it a step further, when the mice were genetically manipulated to lack the prostanoid receptor of interest, the life span increased by 6.7%. It can be reasonably concluded, therefore, that the overexpression of a particular prostanoid receptor is one cause of ALS. This drug, used for inhibiting the receptors, has even managed to circumvent the normal 12 year time difference between discovery and market availability. Since it is already in Phase I clinical trials for the treatment of epilepsy, the process of drug development can be cut shorter. The drug, however, must still be tested for its ability to cross the blood-brain barrier and its effects, positive and negative, on other cells, before it can become a viable treatment option.

This discovery is a considerable breakthrough in finding a treatment for ALS and neurodegenerative disorders in general. The cause for such disorders, as shown by this study, needn’t be housed exclusively in the neuron of interest. Any other cell or molecule taking part in the process of degeneration could possibly be the source of the expressed genetic mutation.

Trying to understand ALS from the biochemistry at a molecular level to the demographics at the global level, researchers have begun to unravel the mystery of the disease and others similar to it. As the medical field progresses, aided by the more comprehensive understanding of biological processes, both the amount and types of diagnoses increase, so much so that it is hard to justify donation to an organization for patients comprising 0.000039% of the nation (in the case of ALS). However, discoveries like this show that donors should not only be motivated by a cure for a specific condition, but also by the hope that discoveries that link several diseases together will be made and that new perspectives and techniques in treatment will be born. The only way that funding for labs can occur, though, is through constant dependence on the awareness of the public and government. In this way, awareness, even if spread by a ridiculous act like dumping ice on others, is meaningful and effective in treating ALS and other diseases, cured by using the same mindset as Eggan’s team.

 

References:

“About ALS.” The ALS Association. ALS Association, n.d. Web. 13 Aug. 2014. “Amyotrophic Lateral Sclerosis (ALS) Fact Sheet.” : National Institute of Neurological Disorders and Stroke (NINDS). NIH, n.d. Web. 12 Aug. 2014. Colen, B. D. “Progress against ALS.” Harvard Gazette. Harvard University, 6 Aug. 2014. Web. 13 Aug. 2014. Johnson, Carolyn Y. “Harvard Researchers Show ALS May Result from Toxic Interaction between Brain Cells – The Boston Globe.” BostonGlobe.com. Boston Globe, 6 Aug. 2014. Web. 13 Aug. 2014.