Tuesday, 28 May 2013

Root Cause Analysis

Does knowing the cause of ALS lead to a cure? If history is any reflection of the answer to this question, then the answer is "not very quickly". That's because this baffling disease is linked to so many other issues, to so many other potential triggers as to make it, to quote that great statesman Winston Churchill when asked about Russia, "a riddle wrapped in a mystery inside an enigma".

In August, 2011, the ALS world was put all aflutter with the new that a study by the Feinberg School of Medicine at Northwestern University had uncovered a common cause of all forms of ALS. The study found that the "basis of the disorder is a broken down protein recycling system in the neurons of the spinal cord and the brain."

"Feinberg scientists found the cause of ALS by discovering a protein, ubiquilin2, whose critical job is to recycle damaged or misfolded proteins in motor and cortical neurons and shuttle them off to be reprocessed."

The study further found that "ubiquilin2 isn't doing its job. As a result, the damaged proteins and ubiquilin2 loiter and accumulate in the motor neurons in the spinal cord and cortical and hippocampal neurons in the brain." In other words the proteins aren't working; they're just hanging around like unemployed waste transfer station workers.

There were articles heralding the potential for a cure and urgings from various quarters for new studies and research. Two years have passed since then and still no cure has been found. Still no treatments have been uncovered. Still no success with drugs and other therapies. This is not particularly surprising. In something as complex as neurodegenerative disease, a cure based on a single element is highly unlikely in a short period of time, nothing short of a miracle, that miracle we all pray for daily.

It is not enough to know that the protein recycling system is failing, there has to be a way to re-trigger the failed system. Researchers need to find out what causes the system to fail and how to link treatment to reversing that underlying cause. It's your basic root cause analysis, asking why after why after why.

On May 26, 2013, Stanford University School of Medicine released a study which "identified mutations in several new genes that might be associated with the development of spontaneously occurring cases of the neurodegenerative disease known as amyotrophic lateral sclerosis, or ALS." Please note the use of the word "might" in that statement. At a minimum this new discovery helps researchers look more closely and improve the efficiency of their research.

Once again researchers are narrowing the focus. Yet once again they need to dig deeper, further investigating the failed protein sequence that these genetic mutations can trigger and the amino acids that are critical in the functioning of these failed proteins. We have a cause and researchers are looking ever more deeply into the why behind that cause. It is still tantalizingly just beyond our grasp.

So we know, mostly, that it is likely a failed protein sequence and that protein sequence is linked to a specific random genetic mutation. We still need to discover why that gene mutates, why the process fails and how to re-trigger the process of recycling those failed proteins. There is yet more work to be done. We still don't actually know the "cause", just symptoms that make up this enigma, needing to be peeled away until the mystery is unwrapped and the riddle can be solved.

We need to ask "why" yet a few more times.


  1. Another interesting article where researchers used a multi-drug approach.


    Since ALS is a systemic disease, single effect drugs will consistently fail. Multiple drugs treating multiple issues will likely have greater chances for success.

  2. oh Rick I know it will be too late for you but I still pray for a miracle. It has been a great visit this past week and I look forward to seeing you soon again.
    much love Mom