What is ALS? And can it be cured?

May 3, 2017 | Trends

When I was about 6 or 7 years old, I watched Stephen Hawking beat Sir Isaac Newton, Albert Einstein and an android in a game of poker.

I’m not kidding, I really did!

Of course it was on an episode of Star Trek: The Next Generation. The android, Data, in an attempt to better understand the various facets of humanity, plays poker with three of the greatest minds in history on a holodeck: Hawking, Newton and Einstein.

After the episode was over, I turned to my mom (an accomplished scientist) and asked her why Stephen Hawking used a robot voice to speak. She went on to tell me what she knew about him, particularly about his ALS, Amyotrophic Lateral Sclerosis, and about how Hawking has survived far longer than most people with ALS do.

Two decades later, Hawking is still alive, has so many letters after his name that it looks like a math equation and has published academic papers in journals as recently as 2016.

Shivering for ALS: The Ice Bucket Challenge

In the summer of 2014, the internet and social media in particular was drowning in ice bucket challenge videos. This challenge led to an upsurge in the public’s awareness of ALS and donations to ALS charities went through the roof. It started with 3 young men who had ALS dumping water on their heads and before we knew it, it seemed like everyone was uploading shivering videos of themselves calling for people to upload their own videos and (hopefully) to donate to ALS research. The money made a difference: a new gene for ALS was discovered. August of each year continues to be ALS month and the ALS Association (ALSA) continues to raise awareness and seek donations.

But what exactly is ALS? And how close are we to a cure?

What is ALS?

ALS, Lou Gehrig’s Disease (US) or Motor Neurone Disease (UK) is a progressive, fatal and neurodegenerative disease distinguished by the loss of motor neurons in the brain and spinal cord. The incidence is about 1 in 7 people or 3.9 cases per 100,00 people with about 12,000 people diagnosed in the US alone. It’s most common in white males between the ages of 60-69 and can be sporadic or familial.

Sporadic ALS (SALS) occurs in about 90-95% of individuals and have no family history or genetic mutations to provoke AlS. Those with familial ALS (FALS)  account for about 5-10% of cases and these have any combination of over a dozen ALS genes. ALS can be autosomal dominant or recessive but the dominant form is more common.

Why haven’t we cured ALS yet?

ALS was first described as far back as 1869. However we still don’t fully understand the disease’s etiology and as of Spring 2017 there is only one FDA approved drug to treat ALS. It’s very tough to study ALS because of how complicated the disease seems to be (below). In addition, most of our research has relied on animal models. Animal models are expensive and the results gained so far have been far from satisfactory. Recapitulating ALS in animal models has cost the US about $700 million and resulted in only one new drug. That drug, Rilutek (riluzole), was approved way back in 1995. In some cases, drugs that slowed the progression of the disease in mice actually accelerated it in humans. We need to understand more about the genes involved, the risk factors, the role played by the environments, what biology plays a part and just what is going on on a molecular level. We also need to diagnose ALS more quickly and we need a way to halt or even reverse the neuronal damage involved.

All over the literature, you’ll read about how ALS is a “complex” disorder but what this actually means goes far beyond, “it’s hard to understand”; we don’t even know if there is one disease called ALS. There may be several very similar and related disorders that are difficult to distinguish and are characterized by neuronal degeneration, paralysis and respiratory and muscular problems and deterioration.

Is ALS like Multiple Sclerosis?

ALS is distinguished from other neurodegenerative diseases like Multiple Sclerosis (MS) and Alzheimer’s Disease (AD) in part by the combination of symptoms it involves:

  • motor neuron loss (lesions)
  • retraction of motor neuron axons from neuromuscular junctions
  • the appearance of inclusion bodies within neurons and astrocytes
  • ubiquitin-positive protein aggregates in neurons
  • blood–brain barrier disruption

The “sclerosis” part of ALS and MS refers to scarring of the coverings on neurons, the myelin sheath. In MS, this sheath is attacked by the body leading to the loss of signals from one part of the body to another. In ALS, the nerve itself is damaged. ALS affects the neurons involved in movement. However MS can affect neurons across the brain from your emotional state, to bladder control to your senses as well as movement. MS is more common in women and ALS in men. MS tends to get diagnoses between age 20-40 whereas ALS is usually diagnosed later in life . ALS also overlaps a lot with Parkinson’s and again the specifics of each cases are key to ensure correct diagnosis. Lastly, patients with ALS usually succumb to ALS within 3-5 years of diagnosis whereas those with MS tend to live to within 5 to 10 years of the average life expectancy of the general public. Those with ALS often pass away as a result of either respiratory or cardiac problems. Historically, a lack of nutrition and water would also results in increased mortality; nowadays the surgical implantation of a feeding tube into patients allowing them to live longer and so this is less of an issue in developed countries.

What ALS clinical trials are happening?

Thankfully, so many! These cover a range of topics including:

  • Stem cells
  • Diets
  • Various drugs
  • Various devices
  • Botox or Botulinum Toxin
  • Protein injections
  • Cannabis Sativa
  • Monoclonal antibodies (like ozanezumab)
  • Immunosuppressants (like fingolimod)

To find an ALS study near you, check out the ALSA’s website.

Special Note (after the initial publication of this blog article):

On May 5th (2017), the FDA approved a drug, Edaravone (brand name: Radicava), under the Orphan designation for treatment of ALS. The drug is delivered via intravenous injections and it was first approved for use in Japan and South Korea in 2015 (by Mitsubishi Tanabe Pharma). Mechanistically, the drug compound is targeting the oxidative stress pathway in neurons as a “free radical scavenger”. Thus, it serves to protect specific types of neurons from neurotoxicities and can slow down the disease progression in certain patients. Clinical trial data released so far suggest that it is most beneficial for early stage (i.e., about ⅓ of the patients can benefit). The drug will be available for patients starting in June 2017.

Article by Olwen Reina. Contact Olwen at olwen@tempobioscience.com.