Amyotrophic lateral sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a rapidly progressive, fatal neurological disease that attacks the nerve cells responsible for controlling voluntary muscles. As many as 20,000 Americans have ALS, and an estimated 5,000 people in the United States are diagnosed with the disease each year. ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. ALS most commonly strikes people between 40 and 60 years of age, but in some cases younger people can also be affected.

The disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away (atrophy), and twitch. Eventually, the ability of the brain to start and control all voluntary movement is lost and patients lose the ability to move their arms, legs, and body. When muscles in the diaphragm and chest wall fail, patients lose the ability to breathe without ventilatory support. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms.

However, about 10 percent of ALS patients survive for 10 or more years. In 90 to 95 percent of all ALS cases, the disease occurs apparently at random with no clearly associated risk factors. About 5 to 10 percent of all ALS cases are inherited. The familial form of ALS usually results from a pattern of inheritance that requires only one parent to carry the gene responsible for the disease. About 20 percent of all familial cases result from a specific genetic defect that leads to mutation of the enzyme known as superoxide dismutase 1 (SOD1). However, not all familial ALS cases are due to the SOD1 mutation; therefore other unidentified genetic causes clearly exist.

ALS research at the Hussman Institute for Human Genomics (HIHG) led by Dr. Margaret Pericak-Vance is multi-faceted. The HIHG researchers collaborate with many different groups and institutions to find the genetic causes of ALS. For more than 20 years, the ALS group has been collaborating with researchers at Vanderbilt University, Massachusetts General Hospital, and Northwestern University to identify the gene(s) which predispose some families to develop ALS. We search for the genetic factors involved in both the familial and non-familial forms of ALS. In addition, we focus specifically on those rare large ALS families that have many family members with the disease. We also study how the environment interacts with genes to cause ALS. Our Collaborative Amyotrophic Sclerosis Study (CALSS) has greatly extended the genetic knowledge of ALS to include genes on chromosomes 9, 16, 18, 20 and X in very large families with many family members with ALS; as well as additional genes on chromosomes 2, 7, 8, 17, 18, and 19 in the smaller and non-familial ALS cases.