Causes of ALS
Amyotrophic lateral sclerosis (ALS), also referred to as Lou Gehrig’s disease, is a neurodegenerative disease that has a wide range of symptoms and potential causes. In more than nine out of every 10 cases diagnosed, there’s no clear identifying cause – most patients don’t have large numbers of affected family members that signal an obvious genetic history.
Nor have scientists been able to find clues about what causes ALS in anything about the way patients live their lives. So far, nothing in patients’ diets, where they’ve lived, how they’ve lived or what they’ve done with their lives seems to explain why they’ve developed this late onset, progressive disease that slowly causes their motor neurons to malfunction and die.
ALS in the Family
In 5 to 10 percent of all ALS cases, a clear genetic history exists. The disease is classed as autosomal dominant in these patients; that is, if a parent carries a genetic mutation that causes ALS, each child has a 50/50 chance of inheriting that mutation and developing ALS.
Studies in the early 1990s on genetic forms of ALS revealed that a single gene defect could account for a portion of these familial cases. Roughly 15 to 20 percent of familial ALS stems from mutations in the gene for the enzymes superoxide dismutase 1 (SOD1) or copper zinc superoxide dismutase. That means approximately 1 to 2 percent of all cases of ALS stem from SOD mutations. Another 3 percent or so of ALS results from mutations in other genes.
In October 2011, an international team of scientists, including Packard researchers, identified the most common genetic cause of ALS in a gene called C9ORF72. In this gene, found on chromosome 9, six letters of the genetic code are normally repeated only a handful of times. In up to 45 percent of those with familial ALS, these six letters are repeated hundreds, even thousands of times. Since this discovery, scientists at Packard and at institutions around the world have been working to figure out how this mutation causes ALS.
Getting at the Cause of ALS
Still, for the majority of ALS cases – known as sporadic ALS – cause is unknown. Something genetic is almost certainly at work, if only for a predisposition to the disease. And some subtle environmental element is also suspected – a toxin, perhaps.
Generally when a patient receives an ALS diagnosis, the disease has been underway for quite some time. Once ALS begins, it spreads throughout the entire central nervous system, both brain and spinal cord.
ALS is primarily an illness of motor neurons. But it’s also one of astrocytes, the common nervous system cells that support motor neurons by providing energy and helping to repair damaged neurons. Throughout the disease, a number of cell processes go awry, contributing to and maintaining ALS’s progress. So far, no single one of them appears far more important than any other.
Packard Center researchers are targeting these pathogenic processes as the best way to understand the cause of ALS and cure it: