Causes of ALS

The causes of ALS disease are not completely understood. And scientists don't know why ALS strikes some people and not others. But in recent years, research has brought a wealth of new scientific understanding regarding this disease.

Years ago, researchers believed that a single cause might explain all cases of ALS. Today, we know that can’t be the case.

Genetics and ALS

Only in rare cases (about 5-10%) is ALS inherited. One parent carrying the gene can be responsible for the disease. This is known as Familial ALS (FALS). However, in most cases the disease occurs apparently at random with no clear risk factors associated with it.

In 1993, scientists discovered a mutation associated with about 20% of the cases of FALS. The mutation was found in the gene that produces the SOD1 enzyme (an enzyme important in antioxidant defense). But 80% of people with FALS don't have the SOD1 mutation. That means some other – as yet unidentified – genetic cause exists.

In August 2007, scientists at the Translational Genomics Research Institute in Phoenix identified several genetic differences in people with ALS compared to those without ALS.

Other hypotheses

In 90-95% of all ALS cases, patients do not have a family history of the disease. Additionally, their family members are not considered to be at increased risk for developing ALS. These cases are considered Sporadic ALS (SALS).

Many clues have pointed to possible causes of ALS. But so far, no single cause or event has been found. Most experts believe that several existing clues are linked to the cause of ALS and each other:

• Free radicals – Cells produce these highly reactive molecules during normal metabolism. Normally, they are neutralized by the SOD1 enzyme, a powerful antioxidant. It's unclear how, but researchers think a faulty SOD1 gene may allow free radicals to accumulate in large doses.
• Glutamate – Studies have shown that neurons begin to die off when exposed to excessive amounts of glutamate – a chemical messenger in the brain. Glutamate is found in higher-than-normal levels in ALS patients.
• Autoimmune responses – When the human body's immune system attacks normal, healthy cells, the body gets sick. Researchers are examining whether antibodies may be interfering with the transmission of signals between the brain and the muscles.
• Neurofilaments – These proteins help nerve cells hold their shape. In ALS, neurofilaments tend to clump up in the body of the cell instead of moving to the axon (the tail of the cell). Such clumping could cause a cellular traffic jam, preventing nutrients and other vital materials from traveling up and down the axon.

In searching for the cause of ALS, researchers have also studied environmental factors such as exposure to toxins or viruses and other infectious agents. Other research has examined the possible role of dietary deficiency or trauma. However, as of yet, there is insufficient evidence to say for certain these factors are causes of ALS.