Partner Research Centers:

Center for Neurodegenerative Disease Research

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive neurodegenerative disease that affects upper and lower motor neurons in the brain and spine, resulting in lost control of the muscles — first those in the arms and legs and eventually the muscles needed for speaking, swallowing, and breathing.

In the United States, more than 5,000 people are diagnosed with ALS each year, and about 20,000-30,000 are living with the disease. It is somewhat more common in men than in women and usually strikes between the ages of 40 and 60, with the incidence increasing with age.


Early in the disease, people experience muscle weakness and fatigue, particularly in the arms and legs, resulting in tripping and dropping things. Other common early signs included slurred speech and muscle cramps and twitches and uncontrollable periods of laughing and crying. Gradually, the weakness and paralysis spread to other muscles, and patients may have difficulty speaking, swallowing, and breathing. Other types of nerves are not affected; thus people with ALS do not lose their ability to see, smell, hear, or recognized touch. Although intelligence is not affected, some people with ALS become depressed or experience memory or decision-making difficulties.

About half of ALS patients live at least 3 years after being diagnosed, and about 20% live more than 5 years. Physicist Stephen Hawking has been living with ALS for 45 years. Though almost completely paralyzed and unable to speak except through a voice synthesizer, he continues to study theoretical physics, travels, and lectures extensively.


The cause of ALS is unknown. The vast majority (90-95%) of ALS cases are sporadic, meaning that they occur randomly rather than being inherited. Although there have been clusters of ALS cases that suggest some sort of environmental trigger such as a toxin or infectious agent, none has been found. Whatever the trigger, the destruction and death of neurons may result from one or more of several possible mechanisms, including aberrant protein aggregation, protein misfolding, neuroinflammation, mitochondrial dysfunction, and oxidative stress and excitotoxicity.

Of the 5-10% of genetic or “familial” cases, about one in five have been found to have mutations in the gene for an antioxidant enzyme called SOD1 (superoxide dismutase 1). Over 120 different mutations in SOD1 have been identified. How these mutations lead to neurodegeneration is not known.

In 2006, CNDR researchers discovered, in the brain tissue of people who had died from sporadic forms of ALS, accumulations of a misfolded protein called TDP-43.  Similar aggregates of this protein were also found in brain tissue from people with Frontotemporal Dementia (FTD).  Now these scientists are trying to understand the basic biology and genetics of TDP-43 and the mechanisms that lead to the formation of aggregates. CNDR scientists have also found two families with familial ALS in which mutations in the gene for TDP-43 tracked with the disease, further supporting the idea that TDP-43 plays an important role in ALS and FTD.

Treating ALS

There is no cure for ALS. The FDA has approved one drug, riluzole, that has been shown to slow the progression of the disease.

Other treatments can help relieve problems associated with ALS; for example, drugs may be given to relive muscle cramping or excess salivation. In addition, patients may benefit from physical therapy, exercise, speech therapy, respiratory therapy, and nutritional counseling. Assistive devices are often used to help with communication, ambulation, and breathing.

Newer and Experimental Treatments

A recent pilot study suggested that lithium, used to treat bipolar disorder, may slow progression of the disease.  Scientists are also investigating many possible experimental therapies, including anti-oxidants, neurotrophic factors that would protect neurons from the neurodegeneration.