What happens in the brain with ALS?

answered by Hannah Walgrave

redactie/vertaling: Marina Boon, Katarina Koch

Short answer

In patients with Amyotrophic Lateral Sclerosis or ALS, the cells that connect the brain with the muscles die. This means that the brain can no longer tell the muscles to move, leading to progressive paralysis. Typically, ALS patients die 3 to 5 years after their first symptoms.

Longer answer

How do you get ALS?

The brain cells that control our muscles are called ‘motor neurons’. They form the long connection from our brain, to the spinal cord and eventually to all muscles in our body. In ALS, these motor neurons degenerate or die, leading to the loss of connection between brain and muscle.

Most cases of ALS are called sporadic, this means that there was no history of ALS in the family of those patients. In about 10% of ALS cases, the patients have relatives with ALS and these cases are called familial. We now know that in both types of ALS, different mutations in the DNA can be the cause of the disease. In familial ALS, these mutations are passed on from generation to generation. In sporadic ALS, the mutation arose by chance. In many cases, the exact genetic mutation that caused the disease is unknown. The extent to which environmental factors play a role in getting ALS is currently being studied. The chance of getting ALS during your life is 1/385.

What causes the death of the motor neurons?

What causes the death of motor neurons is not completely understood yet. However, in the vast majority of ALS cases, toxic aggregates or clumps are found in the cells of patients. These aggregates trap and disable proteins that are essential for normal functioning of the cells and are thus thought to contribute to motor neuron degeneration.

How does the disease progress?

ALS patients gradually lose the ability to instruct their muscles to move. Depending on the type of ALS, patients will first experience weakness in arms or legs (called limb-onset ALS) leading to difficulties in walking or holding something. Sometimes symptoms start in the muscles of the face or neck (bulbar-onset ALS) resulting in slurred speech and difficulty swallowing. In the last stages of ALS, patients lose control over the muscles that are essential for breathing, which will eventually lead to their demise.

Can ALS be treated?

No, currently, ALS is an incurable disease. However, there is reason for hope. Recently (in April 2023), the American Federal Drug Agency approved a new drug for the treatment of a specific genetic form of ALS, for patients with a mutation in the SOD1 gene (around 1% of ALS cases). This new drug, called Tofersen, is currently being evaluated by the European Drug Agency for approval in Europe and could be the first drug that can treat a form of ALS. The approval of Tofersen could pave the way for future drugs that can also treat different forms of ALS.

Read more?

Lifetime Risk and Heritability of Amyotrophic Lateral Sclerosis | Genetics and Genomics | JAMA Neurology | JAMA Network

Risk factors for amyotrophic lateral sclerosis – PMC (nih.gov)