How Cold Buckets Led to Advancing Research

Many of us remember the ALS ice bucket challenge of 2014; the challenge went viral, and people everywhere became aware of a disease that otherwise would have hid in the shadows.  At the time, I personally thought challenge was bad; all I saw was a bunch of teenagers dumping water on each other, not paying any attention to the cause behind it.  Truth be told, the idea behind the challenge, the idea that you could feel what it is like to have ALS for a second, wasn’t true at all; how can a bucket of water represent someone’s body slowly degrading into a motionless state?  The only part I liked about it was the awareness and donations celebrities gave to the cause because that’s where, in my mind, the most beneficial part was.  However, this summer I was taken slightly aback when I saw the headline, “The ALS ‘Ice bucket challenge’ is working”, and I was a bit stunned.  Upon further reading, I discovered that the ALS Association had received $115 million dollars, money they would not have without the challenge.  Furthermore, just $1 million of that total went to Project MinE, a global research project whose aim is “to sequence the genomes of at least 15,000 people with ALS”.  On July 25th, the ALS Association confirmed that Project MinE had discovered an important link between genetic ALS and the NEK1 gene.  Later this year they also announced a possible 1st method of therapy for the genetic variation of the disease.

The Biology

ALS is a neurodegenerative disease that affects the upper and lower motor neurons, degrading the motor nervous system and causing atrophy in muscles until the patient is paralyzed, dependent on family members and nursing care.  The disease is always fatal, usually within 2 to 5 years after diagnosis.  The cause is currently unknown, but several strong leads have surfaced in years past.  Before the discovery of the NEK1 gene, the SOD1 gene (20% of genetic cases) and the FTD2 gene (25-30% of genetic cases) were the most common genes identified linking to ALS.  How much or how vital the NEK1 gene is to genetic ALS remains unknown currently.  Also because of these new advances brought on by the funding provided though the challenge, the first method of therapy is currently being developed for genetic ALS by targeting the gene expansion called C9orf72.  Coded by long repeats of the nucleotide sequence “GGGGCC”, this expansion has been identified to create three toxic entities;  RNA sense and anti-sense molecules, as well as unusual proteins called dipeptide repeat proteins (DPRs).  These three have been the target of therapy in the past, but they were treated individually and did not help much.  The study identified that by targeting the transcription factor called Spt4 (or SUPT4H1 in humans), reduced the expression of long, repeated genes, while leaving short repeated genes alone.  Researchers found that in yeast cells, decreasing the amount of Spt4 reduced sense and antisense transcripts, as well as DPRs, without reducing transcripts from other genes;  when the experiment was put into fly and worms, similar results were found with no other clear signs of toxicity.

These entire results sum up to an amazing advance in fighting ALS, but sadly it is only beneficial to the genetic side of ALS, which makes up a shallow 10% of all types of the terrible disease.  Hopefully, some of this money will be put toward the other 90% of patients with spontaneous ALS, the form my grandfather had before he died two years ago.  My view of the challenge has changed slightly, but I am hopeful that the rest of the money raised can make even more leaps and bounds, and we can finally have the 1st disease cured by a viral video.

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About Mr. Mohn

Biology Teacher

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