ALS awareness is on the rise, thanks to the ubiquitous ice bucket challenges making worldwide headlines. This social media phenomena prompts us here at WEEKLY to wonder: what is this disease and where does the biotech industry stand?

ALS stands for Amyotrophic Lateral Scelerosis. Let’s break it down to its roots:

  • ‘A’ means no
  • ‘Myo’ means muscle
  • ‘Trophic’ means nourishment

“No muscle nourishment” means just that: motor neurons tasked with sending impulses to the muscles cannot do their job because they are degenerating. “Lateral” means side, indicating where the motor neurons are located within the spinal column. “Scelerosis” refers to the scarring that occurs in the region of the degenerating neurons. Because ALS affects the motor neurons (or neurons that control muscle movement), disease symptoms start with muscle weakness and progress to paralysis, eventually eroding the patient’s ability to walk, chew, swallow, speak, and in advanced stages, breathe.

Thanks to this viral campaign, the ALS Association has raised more than $100 million and recruited more than two million new donors to date, setting a precedent for rare disease fundraising efforts. Now that the ice cubes have started to melt, we will take a look at the science behind the awareness.


Approximately 90% of ALS cases are of unknown origin. The other 10% are associated with FALS, or Familial Amyotrophic Lateral Sclerosis. Drug discovery is difficult for diseases whose mechanisms are not well understood or unknown. ALS is complex with many factors potentially contributing to the demise of various organ systems via motor neuron death.

The most prominently identifiable culprit is one of several different mutations in a gene located on chromosome 21, known as SOD1. It encodes for superoxide dismutase, an antioxidant enzyme that helps cells get rid of excessive free radicals. Research suggests ALS is not actually associated with free radicals, leaving the exact role of SOD1 mutations unanswered. In some cases of sporadic ALS, incorrectly folded versions of the SOD1 protein have been detected, even though there is no genetic mutation.


Rilutek, marketed by Sanofi (Paris, France) is the only FDA approved therapy for ALS. Rilutek is thought to work by acting as a glutamate inhibitor, although the exact mechanism of action is not known.

A buildup of a neurotransmitter—a chemical produced by the body that transmits messages between nerve cells—called glutamate has been observed in the early stages of ALS. Glutamate is involved in activating motor neurons. One theory is the excessive glutamate somehow damages the motor neurons by overstimulating them. Rilutak potentially blocks the glutamate. While it is not a cure for ALS, it may extend life by approximately sixty 60 to 90 days and possibly slow overall disease progression.


Prior to last month’s ALS campaign, the disease was commonly known as Lou Gehrig’s disease, referring to the Yankee’s baseball player. Lou Gehrig died in 1941 at age 37 after being diagnosed with the disease on his 36th birthday. The disease normally progresses very rapidly (Lou Gehrig died almost two years after being diagnosed). On the opposite end of the spectrum is 72-year-old physicist Stephen Hawking, a living example of how the disease can progress very slowly. Diagnosed at age 21, Hawking’s specific case illustrates how mental function is typically not impacted by ALS.



There is plenty of interest in developing ALS treatments with Biogen Idec (Cambridge, MA) announcing an “ALS Innovation Hub” last month—an effort to better understand the disease mechanism with the goal of identifying new drug targets. And Prize4Life (Berkeley, CA) is inviting academic and industry contenders to compete in finding a treatment for ALS. One million dollars will begiven to the winner. Founded in 2006, Prize4Life’s goal is to “accelerate the discovery of treatments and a cure for ALS.” Registration is still open. Could we have a winner from one of the treatments listed below?

ISIS Pharmaceuticals (Carlsbad, CA) announced positive results from a Phase I study of an antisense drug targeting the SOD1 gene last year. The drug is aimed at FALS and approximately 20% of FALS cases are tied to the mutated SOD1 gene.

Neuralstem (Germantown, MD) is currently conducting Phase II studies on a stem cell treatment for ALS. Human spinal cord stem cells are surgically implanted into ALS patients—where the cells differentiate into motor neuron cells, essentially repairing the damaged nerves that are the source of the disease. Phase II results have not yet been announced, but stem cell treatment showed promising results in an animal model of the disease.

GlaxoSmithKline is in Phase II trials with monoclonal antibody Ozanezumab, aimed to maintain existing muscle function in ALS patients with the possibility of slowing the progression of the disease.

Lastly, ALS Therapy Development Institute (ALS TDI) (Cambridge, MA) screens over 25 different therapies targeting ALS, check out their active pipeline.

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