The Science of ALS and the Irony of the Ice Bucket Challenge

With the ALS ice bucket challenge going viral, amyotrophic lateral sclerosis (ALS) has been getting a lot of attention. But what exactly is ALS? It is essentially a poorly understood neurodegenerative disease that kills relatively quickly — with people usually dying within 3–5 years after onset of the first symptoms — and is responsible for the death of about 2 out of every 100,000 people in the U.S. And most people with ALS (90% of them) have no family history with the disease — why they get ALS is unclear.

So what makes the ice bucket challenge ironic? Several lawmakers have chosen to participate in the challenge even though they previously significantly cut funding for research into the disease.

“Amyotrophic” is basically Greek for “no muscle nourishment.” In ALS (also called Lou Gehrig’s disease after the famous baseball player who died to the disease), the muscles become weakened and damaged due to specific neurons degenerating. The initial symptoms can include trouble swallowing, speaking, and/or breathing, as well as having stiff muscles (in arms, legs, or elsewhere). Sometimes a specific arm or leg is most affected. A person with ALS can also have exaggerated reflexes, such as an overactive gag reflex, twitches, cramps, and exaggerated emotional expressions. As the disease progresses and the muscles weaken, most people with ALS cannot use their arms, walk, speak, swallow food, or breathe on their own (and need a ventilator). This is why most individuals die due to respiratory failure, and only 4% of people survive for more than 10 years after onset of symptoms. Stephen Hawking, who has had ALS for more than 50 years, is one of these rare cases.

On a molecular level, how does the disease cause these symptoms? It is unfortunately poorly understood (which is why the field is in such need of funding). There are some suspected culprits, but few (if any) definitive cause-and-effect relationships. For example, some proteins that are important for holding cells and tissues together and allowing them to communicate properly (i.e., laminins, which are extracellular matrix proteins) are not being made in the right amounts in some muscles. Researchers have also found that some muscle fibers are (unsurprisingly) damaged in limbs and connective tissue may be produced by the body to try and compensate for this damage, while nerve patterns may also try to re-wire themselves due to the disease.

For the 90% who do not have a family history of ALS, there are no known causes for certain, but there are some suspects. Several of these include possible physical trauma, such as head trauma (with damage to certain motor system areas), playing in contact sports, and military service. (This may be why several famous football players have had ALS.) Diet is also thought to be a possible factor, such as eating food contaminated by blue-green algae. Frequent drug use, being exposed to electromagnetic fields, and experiencing electric shock may also be related to contracting ALS, but these connections are unclear.

There is at least a clear suspect for familial cases of ALS — for 20% of familial cases (or around 2% of all ALS cases) there are mutations associated with an important antioxidant. The antioxidant, which is superoxide dismutase, helps turn a potentially dangerous toxin (superoxide made by the body) into oxygen and hydrogen peroxide. (Interestingly, some research suggests that people who eat fruits and vegetables that have antioxidants, specifically carotenoids, may have a reduced chance of getting ALS — carotenoids are in carrots, pumpkins, sweet potatoes, watermelon, tomatoes, grapefruit, papaya, apricot, guava, kale, dandelion leaves, turnip greens, spinach, peas, lettuce, zucchini, Brussel sprouts, broccoli, and more.) Currently, a large genetic study, called Project MinE, is being crowd-funded to better understand the genetics of ALS.

Right now, the only treatment for ALS is Riluzole (i.e., Rulutek), and this drug typically only improves survival by a few months. It does not reverse any damage already done. That said, there are several ongoing clinical trials to treat ALS. One of these uses a patient’s bone marrow stem cells, turning them into different neuronal cells and then having those injected into specific muscles in the patient.

Despite there being few treatment options for ALS (and other rare diseases), the National Institutes of Health (NIH) had to cut $1.55 billion from its budget due to a compromise by the White House and Congressional Democrats to get Congressional Republicans to pass the debt ceiling hike. Among that $1.55 billion cut was millions of dollars for ALS research. Specifically, this caused ALS research funding to decrease from $44 million in 2012 to $39 million in 2013, or a decrease of $5 million. Ironically, several lawmakers who cut this ALS funding have recently undertaken the ALS ice bucket challenge. The challenge has raised about $80 million (as of August 25, 2014), compared to about $2.5 million raised during the same time frame in 2013. This easily compensates for the $5 million lost due to cuts, but the donations do not go through NIH.

So while this viral fundraising activity has significantly helped raise money for ALS research (and awareness of the disease), more is needed for scientific research on ALS and similarly devastating diseases to be successful. Clinical studies, and other important research efforts, typically span multiple years, so it’s essential to have consistent sources of revenue (i.e., reliable government funding programs) over long periods of time too.

For further reading:

• Bob Grant’s article “Ice Bucket Challenge Irony”
• Sam Stein’s article “Lawmakers Who Cut Funds for ALS Research Take Ice Bucket Challenge for ALS Research”
• The ALS Association’s webpage
• Teisha J. Rowland’s book Biology Bytes: Digestible Essays on Stem Cells and Modern Medicine