How ALS (Lou Gehrig's Disease) Works

ALS is extremely rare, affecting only about two out of every 100,000 people, according to the ALS Association [source: ALSA]. About 5,600 people are diagnosed with the disease in the U.S. each year, and between 20,000 and 30,000 people live with it at any one time [source: ALSA].

What exactly causes ALS isn’t known, but researchers are learning more about the disease all the time. In most cases (90 to 95 percent), there is no known cause, and the disease is called sporadic ALS. In the remaining cases (5 to 10 percent), the disease is passed down through families, and is called familial ALS. A child who is born to someone with familial ALS has a 50 percent chance of also getting the disease [source: ­­ALSA].

Researchers have been looking for the gene or genes responsible for familial ALS, and in 1993, they made a huge breakthrough. They discovered a change or mutation in a gene called superoxide dismutase (SOD1). When the gene is normal, it directs the production of an enzyme that protects the motor neurons from damage caused by unstable molecules called free radicals. When the gene is mutated, the enzyme can’t protect the motor neurons, and they become damaged by the free radicals. About 20 percent of people with familial ALS have the SOD1 gene mutation. Researchers are still looking for more genes that might be involved.

Researchers also know that ALS is most common in Caucasian males, and it often starts when people are between the ages of 40 and 60 (although it can strike at an earlier age). People with ALS have too much of a substance called glutamate in their blood and spinal fluid. This chemical messenger helps nerve cells in the brain and spinal cord communicate with one another, but in large amounts it can actually damage motor neurons.

Researchers have speculated on several other possible causes of ALS, including:

However, there isn't enough evidence from scientific research to prove any of these theories.

When ALS begins, its symptoms are often hard to notice. Some people may become clumsier than usual. Others may experience muscle weakness or stiffness. Still others may slur their words.

Which symptoms appear first depends on the muscles affected. When the disease damages lower motor neurons, muscles in a particular part of the body (like the hand or foot) will be affected. When ALS impacts upper motor neurons, people will experience general clumsiness, slurred speech and difficulty swallowing. Eventually, the disease will spread to all of the body's muscles and lead to total paralysis.

In the early stages of the disease, symptoms may include muscle weakness in one part of the body (an arm or leg); clumsiness, such as tripping and dropping things; difficulty speaking or swallowing; muscle twitches (fasciculations) and cramps; fatigue in the arms or legs; weight loss and the loss of muscle mass; and uncontrolled laughing or crying, called emotional incontinence.

How the disease progresses varies from person to person. But as it worsens, people may experience shortness of breath or difficulty breathing, stiff muscles and exaggerated reflexes (including a strong gag reflex).

Eventually people may lose the ability to breathe on their own and will need to be put on a ventilator. Most people with the disease eventually die from respiratory failure or pneumonia -- because they can't swallow properly, they aspirate food and fluid into the lungs.

While ALS can devastate the body, it doesn't affect involuntary muscles (such as bowel and bladder function), the senses (smell, taste, hearing and sight), or the ability to think.

ALS isn't an easy disease to diagnose. Its symptoms mimic those of other diseases (such as Parkinson's) and there isn't one test to spot it. Often doctors will rule out other diseases to arrive at a diagnosis. For the very small percentage of people with familial ALS, there's a genetic test to look for the faulty SOD1 gene. However, because most people with ALS don't have this gene, the test isn't very useful.

Some tests that are used to diagnose ALS include:

Once a person is diagnosed, the average survival time is only three to five years. However, about 10 percent of people with ALS live for 10 years or more, and the lifespan for ALS patients is increasing as new treatments are introduced [source: ­ALSA].

Today there's no cure for ALS, but researchers are working in that direction. In the meantime, treatments are available to relieve symptoms and improve patients’ quality of life. One of the main therapies focuses on the chemical messenger, glutamate, which ALS patients produce in excess. The drug riluzole (marketed under the brand name Rilutek) decreases the release of glutamate to prevent it from damaging motor neurons. Although it can’t reverse the course of the disease, Rilutek can slow it down, and it has been shown in scientific studies to help ALS patients live for a few months longer than they would otherwise. Other medications help manage the symptoms of ALS -- for example, drugs that treat fatigue, muscle cramps, pain and sleep problems.

Other therapies that can help ALS patients include physical therapy and exercise such as walking, biking and swimming to improve strength and mobility in the unaffected muscles. A walker, brace or wheelchair can help people get around once they're no longer able to walk on their own. And a speech therapist can teach patients techniques to help them speak more clearly.

In some people with ALS, the disease simply stops progressing. It just “burns out.” Doctors don’t know why this happens.

Researchers are always looking for new ways to prevent and combat ALS. Here are a few of the breakthroughs on the horizon:

Researchers are looking for more genes that cause the disease, as well as the factors that cause motor neurons to die.

Scientists are testing out various substances in patients with ALS, including the enzyme SOD1, antioxidants and neurotrophic factors (chemicals in the brain and spinal cord that help neurons develop and protect them). Drugs that might one day be used to treat ALS include the antibiotic minocycline (Minocin), the breast cancer drug tamoxifen, and the antioxidant coenzyme Q10.

Stem cells are another active area in ALS research. In 2008, scientists were able to reprogram stem cells so that they formed healthy motor neurons. They took the cells from the skin of an 82-year-old woman and her 89-year-old sister, both of whom had the SOD1 gene mutation. Scientists hope they might one day be able to use stem cells to replace damaged motor neurons in ALS patients.