What Causes ALS?

What we do know about ALS

There is a lot we know about Amyotrophic Lateral Sclerosis (ALS). The researchers at the ALS Therapy Development Institute (ALS TDI), and around the world, are constantly working to better understand this disease. We know that ALS is a progressive neurodegenerative disease that attacks motor neurons in the brain and spinal cord, resulting in the wasting away of muscle and loss of movement. We know that it can affect anybody at any point in their lives, although it typically affects people between the ages of 40-70. While rare, it can affect people in their 20s or even earlier. We know that before the age of 65 the rate of incidence is slightly higher in men than in women, but over the age of 70 incidence appears to be the same. However, despite knowing so much about who the disease affects and how it affects them, there is still a lot we don’t know, including what causes it.

Is ALS caused by genetics?

Approximately 10 percent of all cases are known as familial ALS. This means that the disease is inherited and passed down from one generation to the next and can usually be traced to a specific gene with a mutation. In 1993, the SOD1 gene became the first gene to be known to be associated with ALS. Now, we know that over 30 genes have an association with ALS. The most common gene associated with ALS is C9orf72 which accounts for 30 to 40 percent of all familial ALS cases. SOD1 accounts for roughly 20 percent of familial cases. Specific mutations of these genes make it so that the gene does not properly function within the body, however, why these mutations lead to a person developing ALS remain unclear. Each gene has their own unique set of mutations – more than 100 mutations in the SOD1 gene have been implicated in ALS – so there are many different theories as to why these mutations cause ALS. While familial cases can be traced back to a specific gene, they make up a minority of all ALS cases, and the majority of cases can’t be traced to a single specific cause.

What causes the other 90% of ALS cases?

The other 90 percent of cases are known as sporadic ALS and occur in people who have no known history of the disease in their family. For a full comparison of familial and sporadic ALS, please read here, https://www.als.net/news/science-sunday-familial-vs-sporadic-als/. Although the exact cause of sporadic cases remains unknown it is commonly believed to be a combination of both genetic and environmental factors and research continues to be done to pinpoint potential causes. Some theories about processes that drive sporadic ALS include oxidative stress, mitochondrial dysfunction, immune system overactivity, glutamate excitotoxicity and accumulation of protein aggregates. Researchers are also studying the roles that environmental factors may play in causing ALS. These environmental factors include exposure to toxic or infectious agents, like viruses, diet, physical trauma and occupational factors. Studies have shown that people who have served in the military are more likely to develop ALS than the general public, however, the “why” for this correlation remains unclear.

It’s important to note that familial and sporadic ALS cases are generally indistinguishable from each other clinically. As researchers continue to explore what exactly causes ALS to better inform drug discovery, breakthroughs in one type of ALS may benefit those who have another form as well.

To learn more about ALS and what researchers at the ALS Therapy Development Institute are doing to find treatments and cures please visit https://www.als.net/als-research/