Amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) is a progressive neuromuscular disorder which attacks nerve cells that lead from the spinal cord to muscles throughout the body. When these motor neurons die, the brain can no longer control muscle movements; in the later stages of the disease, patients become totally paralyzed.
First described in 1869 by French clinician Jean-Martin Charcot, ALS is a misunderstood illness. Doctors once thought it was rare but now consider it fairly common: about 5,000 people in the U.S. are diagnosed with ALS each year. In total there are about 30,000 ALS patients in the U.S. and approximately 5,000 in the United Kingdom. Most people who develop ALS are between the ages of 40 and 70 but the disease strikes younger and older patients as well. Some well-known people who suffered from ALS include British actor David Niven, baseball player Lou Gehrig, Russian composer Dimitri Shostakovich and Chinese leader Mao Zedong. Researchers have found unusual clusters of patients with the disorder among Italian soccer players, veterans of the Persian Gulf War and residents of the island of Guam.
People usually succumb to the disease within three to five years after the diagnosis. But Stephen Hawking, the renowned physicist at Cambridge University, had lived with ALS for more than 40 years, and was still making major contributions to the fields of cosmology and quantum gravity despite his physical handicap. Moreover, investigators have recently made great progress in determining how motor neurons die in ALS patients. In the near future, scientists may develop therapies that could retard the progress of ALS and perhaps even prevent its onset. The most common form of ALS is called sporadic because it appears to strike randomly, targeting anyone in any given place. Familial ALS refers to a particular form of the disease that is inherited, but only about 5 to 10 percent of all patients fall into this category. The early symptoms of the disorder vary from one individual to another, but they usually include dropping objects, tripping, unusual fatigue in the arms or legs, difficulty in speaking, muscle cramps and twitches. The weakness makes it hard for patients to walk or use their hands for daily activities such as washing and dressing. The disease eventually hampers swallowing, chewing and breathing as the weakening and paralysis spreads to the muscles in the trunk. Once the muscles responsible for breathing are attacked, the patient must be put on a mechanical ventilator to survive.
Because ALS harms motor neurons only, the senses of sight, touch, hearing, taste and smell are not affected. For unknown reasons, the motor neurons responsible for movements of the eyes and bladder are spared for long periods. Stephen Hawking, for example, still has control of his eye muscles; at one time he communicated by raising an eyebrow as an assistant pointed to letters on a spelling card. So far only one treatment for ALS has been approved: riluzole, a molecule that can prolong survival by several months, most likely by curbing the release of glutamate by nerve terminals.
What do we know about the causes of this horrible disease? A vast number of theories have been put forward to explain its origin, including infectious agents, a faulty immune system, hereditary sources, toxic substances, chemical imbalances in the body and poor nutrition. A breakthrough came in 1993 when a consortium of geneticists and clinicians discovered a gene that was responsible for one form of hereditary ALS that is responsible for approximately 2 percent of all cases. This gene turned out to code for an enzyme called superoxide dismutase (SOD1) that protects cells from damage caused by free radicals (highly reactive molecules with unpaired electrons). Researchers subsequently identified more than 100 different mutations in the SOD1 gene that cause motor neuron disease. It remains a mystery, though, how alterations in this ubiquitously expressed enzyme can produce such specific damage to one type of cell in the nervous system
Although the SOD1 mutation has taught us a great deal about the familiar forms of the disease, we still need the key to the sporadic cases of ALS.