- The Story of How this Challenge Began
- How Baseball and the “Big Bang” are Connected to this Challenge
- How a Dearth of Genetic Understanding Led to Crowdfunding ALS Research
- The First Drugs May be on the Horizon
How It Began
For those very few of you who have for some reason been disconnected from mainstream and social media, the ALS Ice Bucket Challenge involves dumping a bucket of ice water on someone’s head to promote awareness of the disease amyotrophic lateral sclerosis (ALS) and encourage donations—typically $100—to research ALS. The challenge dares nominated participants to be recorded having a bucket of ice water poured on their heads, and challenging others to do the same. A common stipulation is that nominated people have 24 hours to comply or forfeit by way of a charitable financial donation.
Those of you already familiar with the ALS Bucket Challenge may, however, not know that it was first issued by golfer Chris Kennedy to his cousin Jeanette Senerchia of Pelham, New York, whose husband, Anthony, has had ALS for 11 years.
According to a local newspaper story, Jeanette Senerchia, 40, said “I was going to donate,” but they were really relentless with their texts counting down the time.” When she finally poured icy water on herself, having her 6-year-old daughter Taya record it, she posted the video on Facebook and “it went crazy,” she said. In a little more than a week, 1,000 people across the country, in Canada, Europe and Japan had joined in.
Soon the challenge circled back to Pelham, where Town Supervisor Pete DiPaola took a dousing, along with Town Councilman Timothy Case and Court Clerk Fran Ardisi. State Assemblywoman Amy Paulin and Westchester County Legislator Jim Maisano also got in on the act.
Girl Scouts from Troop 1662 did the honors in front of Town Hall, pouring the water from giant, 5 gallon Home Depot buckets baring the words “Let’s DO this.”
In drought-stricken regions a cool—pun intended—variant has been proposed as seen in this video wherein San Luis Obispo, California photographer Brittany App—yes, it’s really her last name—has a compromise: instead of dumping a bucket of ice water on one’s head, she is challenging people to live on only 5 gallons of water for a day.
BTW, lest we get caught up in all the fun associated the ALS Ice Bucket Challenge, keep in mind that ALS currently has no cure and affects an estimated 350,000 individuals around the globe, killing more than 100,000 annually. The disease can impact anyone, anywhere, regardless of age, ethnicity, or socioeconomic background.
Famous Persons with ALS
While I will echo the last sentences again, it’s apparent that society in general has a fascination—for lack of a better word—in knowing which famous persons have reached a certain age, or married, or passed away, or become afflicted with a disease. In the case of ALS, a website lists a number of such persons among which the most famous are American baseball great Lou Gehrig and British theoretical physicist Stephen Hawking. Captions for their photos below provide further information about each of these two “professional polar opposites” who nevertheless have ALS in common.
ALS Genetics in Brief
Given that this blog deals with “all things nucleic acids,” it’s apropos to mention a bit about the genetics, but quickly add that they are quite complex, as can be read about here.
There is a known hereditary factor in familial ALS. A defect on chromosome 21, which codes for superoxide dismutase, is associated with ~20% of familial cases of ALS, or about 2% of ALS cases overall. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical generated in the mitochondria. Free radicals are highly reactive molecules produced by cells during normal metabolism. Free radicals can accumulate and cause damage to DNA and proteins within cells.
This mutation has over 100 different genotypes. The most common ALS-causing mutation is a mutant SOD1 gene, seen in North American patients; this is characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A-SOD1, is more slowly progressive than typical ALS and patients with this form of the disorder survive for an average of 11 years.
In 2011, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9orf72, which is associated with ALS combined with frontotemporal dementia ALS-FTD, and accounts for some 6% of cases of ALS among white Europeans. The gene is also found in people of Filipino descent.
I found it rather surprising that, where no family history of the disease is present—i.e., in a whopping ~90% of cases—there is no known cause for ALS! How stressful it must be to be afflicted with a disease having no known cause and no drug. Consequently, it’s easy to understand the importance of raising more research funding through the ALS Ice Bucket Challenge, and other money raising endeavors such as the following.
Crowdfunded ALS— Project MinE
I’ve previously commented here on the rapidly growing popularity of crowdfunding as a new, socio-web-based mechanism for “reaching out” to obtain money for conducting scientific research—including ALS. Project MinE is an independent, large-scale, whole-genome research project that has been initiated by two Dutch individuals with ALS and started on World ALS day (June 21) last year. These individuals provide their personal views on Project MinE at their Treeway website, which provides several modes of “communal contributing” that include jumping into Amsterdam canals (!!) as well as the now “classic” Ice Bucket Challenge.
Project MinE is a research project aimed at systematically interrogating the human genome for common and rare genetic variation in ALS—aka genetic “data mining.” The project will involve obtaining donated-DNA sequence information for 15,000 ALS samples and 20,000 healthy controls to obtain a large number of single-nucleotide polymorphisms (SNPs). This and additional sequencing will be performed on a sample size large enough to reliably analyze whole genome sequencing data outside of a family context.
The long-term benefit of the approach taken for project MinE is a catalogue of many non-ALS whole genomes that can be used to investigate other human diseases, including Diabetes Mellitus, some types of cancer, and other neurological disorders. Project MinE is the largest genetic study worldwide for ALS and was started in the second quarter of 2013. Complete information—and details on how to donate may be found at the Project MinE website, which I encourage you to visit.
Harvard Team Reports Possible ALS Drug Target
I thought it would be best to end this post on a positive note—specifically a possible drug target for ALS that is the subject of an online account by Cynthia Fox in Drug Discovery & Developement. Snippets of this exciting story are as follows.
A Harvard University team reported they may have found an ALS therapy—or two! When they blocked a gene for prostanoid receptor DP1 in ALS brain glia cells in a dish, neurons made from human embryonic stem (ES) cells were “completely protected” from death.
When they created ALS mice with that same gene deleted, the mice lived 6.7 percent longer.
This helps validate the idea that neurons made from human stem cells—in a dish—can be drug screens, team leader Kevin Eggan told a press conference. The 6.7 percent survival increase may rise even more, he said, if/when their DP1 antagonist is given with a drug his team earlier found has anti-ALS properties. And as both drugs are FDA-approved for other indications, clinical trials could move fast.
“We think this is a significant advance—both in terms of the use of stem cells for understanding disease, and with respect to understanding the degenerative processes of ALS and how we might inhibit them,” said Eggan.
Let’s all hope that this all proves to be true, and soon!
As always, your comments are welcome.