What is ALS?

Abby, Elias and Dr. Janice Robertson of the Tanz Centre for Reserach in Neurodegenerative Diseases (University of Toronto), explain what ALS is and why research is important today.

(via Tanz Centre for Research in Neurodegenerative Diseases)
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is the most common form of motor neuron disease, affecting approximately 2 per 100,000 individuals, with the prevalence rates of about 1-2 per 10,000. 

A definitive diagnosis of ALS is given according to the criteria of El Escorial. This process can take several months as other potential (less severe) causes of disease are considered before a final diagnosis of ALS is given.

ALS attacks the motor neurons of the brain and spinal cord. These neurons are responsible for voluntary muscle movements such as talking, walking, swallowing and breathing. Disease generally starts as a mild muscle weakness that progresses to paralysis and eventual death, usually within 2-5 years from diagnosis. Currently there is no cure and no truly effective treatment, riluzole being the only currently available FDA-approved medication for ALS.

 

More simply…
ALS is a disease that has to do with how your brain relays messages to your muscles. There are specific nerve cells, called motor neurons, these die and are no longer able to bring messages from your brain to your muscles.

This causes your muscles to stop working.
It is progressive, which means, it may affect your legs today, but tomorrow it may affect your arms and fingers, and so on.

 

It does not stop.

For many, what is not affected is your brain*. Many people who live with ALS describe the disease as being trapped in your own body.

* Read below about ALS and Frontotemporal Dementia.

More About ALS

Anyone can develop ALS.

ALS is NOT contagious. You cannot get it from being around someone who has it. There is a small percentage (5-10%) of cases that are inherited. This is called Familial ALS. All other cases are considered sporadic.

ALS usually strikes people between the ages of 40 and 70 years, however, there are rare cases of younger and older adults.
ALS is usually fatal within two to five years of diagnosis.

 

Two types of ALS

There are two different types of ALS, sporadic and familial. Sporadic, which is the most common form of the disease in Canada and the U.S., accounts for 90 to 95 percent of all cases. It may affect anyone, anywhere. Familial ALS (FALS) accounts for 5 to 10 percent of all cases in Canada and the U.S. Familial ALS means the disease is inherited. In those families, there is a 50% chance each offspring will inherit the gene mutation and may develop the disease.

 

How do you know you have ALS? What are the symptoms?

Each person and each case is different. For Christopher Chiu (ALS Double Play’s inspiration), it started with his toe stubbing on the volleyball court along with slower reaction times. Soon there was tightness in his leg with the feeling that he could not stretch it out. Then his leg would spontaneously give way and he would fall. For others it could involve muscle weakness, twitching, cramping.

 

The rate at which ALS progresses can be quite variable from one person to another. Although the mean survival time with ALS is three to five years, many people live five, 10 or more years. Symptoms can begin in the muscles that control speech and swallowing or in the hands, arms, legs or feet. Not all people with ALS experience the same symptoms or the same sequences or patterns of progression. However, progressive muscle weakness and paralysis are universally experienced.

 

Gradual onset, generally painless, progressive muscle weakness is the most common initial symptom in ALS. Other early symptoms vary but can include tripping, dropping things, abnormal fatigue of the arms and/or legs, slurred speech, muscle cramps and twitches, and/or uncontrollable periods of laughing or crying.

 

When the breathing muscles become affected, ultimately, people with the disease will need permanent ventilatory support to assist with breathing.

 

Since ALS attacks only motor neurons, the sense of sight, touch, hearing, taste and smell are not affected. For many people, muscles of the eyes and bladder are generally not affected.

So what happens?

As the motor neurons die and stop relaying messages to your muscles, all your voluntary muscles become paralyzed; you cannot use them. Your voluntary muscles are all the ones you use at your will, your fingers you use to type and text, your legs to walk, etc. This means that eventually, you cannot walk, feed yourself, dress yourself, and even talking and breathing become difficult.

 

ALS Discovery

ALS was first found in 1869 by French neurologist Jean-Martin Charcot, but it wasn't until 1939 that Lou Gehrig brought national and international attention to the disease. Ending the career of one of the most beloved baseball players of all time, the disease is still most closely associated with his name.

ALS Genetics

Approximately 5-10% of cases are genetically inherited (Familial ALS or fALS) with the remaining 90-95% of cases occurring sporadically (Sporadic ALS or sALS), with no known cause of disease.

The most well established cause of fALS is mutations in the gene encoding copper-zinc superoxide dismutase (commonly known as SOD1), responsible for approximately 15-20% of fALS cases, which corresponds to about 1-2% of all ALS cases. SOD1 is a ubiquitously expressed enzyme that acts by removing toxic superoxide radicals generated via normal biological processes, and that can cause harm to the cell.

Over 100 different mutations have been identified in the SOD1 gene. It remains unclear how these mutations cause the disease as in most cases normal SOD1 enzymatic activity is not affected. Therefore, disease is not caused by an inability of SOD1 to remove toxic superoxide radicals. Instead the mutations appear to impart a gain of toxic function to the SOD1 protein. The nature of this toxicity remains unknown but may be linked to the increased propensity for mutant forms of SOD1 to misfold and to aggregate.

Other genes associated with ALS, but less well established, are Alsin (ALS2), Senataxin (SETX), and Vesicle-Associated Membrane Protein B (VAPB). These genes cause less typical forms of ALS. Mutations in the genes encoding Angiogenin (ANG), Dynactin-1 (DCTN1), Neurofilament heavy subunit (NEFH), or Peripherin (PRPH) appear to increase the risk of developing amyotrophic lateral sclerosis. Recently, mutations in the gene encoding TAR-DNA-Binding protein (TDP-43) have been found in fALS and sALS cases.

Frontotemporal Dementia

About 5-10% of people with ALS also develop frontotemporal dementia (FTD), a destruction of neurons in the brain that causes profound personality changes and disability. The two diseases are similar in both pathology and genetics. FTD tends to affect people earlier than Alzheimer’s disease, the most common type of dementia.

*Information from: http://www.alsa.org/about-als/symptoms.html Current as of November 3, 2021