ALS, or amyotrophic lateral sclerosis, is a motor neuron disease. It attacks the nerve cells responsible for voluntary movement, progressively destroying them until the brain can no longer send signals to the muscles. Also known as Lou Gehrig’s disease, ALS affects both the upper motor neurons (in the brain) and the lower motor neurons (in the spinal cord), which is what distinguishes it from other neurological conditions that target only one set.
How ALS Damages the Body
Motor neurons are the wiring between your brain and your muscles. When you decide to lift your arm, walk across a room, or swallow food, motor neurons carry that instruction. In ALS, those neurons gradually die. As they disappear, the muscles they control weaken, shrink, and eventually stop working entirely.
The underlying damage involves several overlapping problems at the cellular level. One major issue is that toxic protein clumps build up inside nerve cells. Healthy cells have cleanup systems that break down and remove damaged proteins, but in ALS these systems malfunction, allowing harmful protein deposits to accumulate and poison the neuron from within. At the same time, excess levels of a chemical messenger called glutamate overstimulate nerve cells, contributing to their death. Chronic inflammation in the brain and spinal cord further accelerates the damage.
Importantly, ALS does not typically affect thinking, memory, or the senses. You can still see, hear, and feel touch. The disease targets voluntary muscles, the ones you consciously control, which is why it eventually impairs walking, speaking, eating, and breathing.
Sporadic vs. Familial ALS
Most people with ALS have no family history of the disease. This form, called sporadic ALS, accounts for roughly 80% to 90% of cases. The remaining 10% to 20% are familial, meaning the person inherited a gene mutation that causes or increases risk for the disease. Some research suggests the true rate of familial ALS may be closer to 20% when extended family members with related conditions are counted.
Among the genetic forms, one mutation dominates. A specific expansion in a gene called C9orf72 accounts for the vast majority of inherited cases. In one Irish population study tracking ALS genetics over two decades, C9orf72 mutations were responsible for 89 out of 94 cases linked to a known gene. Other gene mutations, including SOD1, FUS, and TARDBP, are far less common but still clinically significant, particularly because one FDA-approved therapy now targets SOD1 specifically.
Who Gets ALS
ALS is relatively rare. In the United States, the incidence is about 1.44 new cases per 100,000 people each year, and the overall prevalence as of 2025 is 10.1 per 100,000. It most commonly appears between ages 55 and 75, and men are slightly more likely to develop it than women.
Beyond age and sex, certain environmental and occupational exposures appear to raise risk. A CDC-affiliated study found that self-reported exposure to pesticides, solvents, or heavy metals roughly doubled the odds of developing ALS. Working in industries with higher chemical exposure, such as construction, manufacturing, or painting, carried nearly four times the risk compared to less-exposed occupations. Even frequent participation in certain water sports, particularly water skiing, showed an independent association with higher ALS risk, though the reasons remain unclear. These findings held up even after adjusting for age, sex, and smoking.
How Symptoms Begin
ALS starts in one of two ways, and where it begins shapes the early experience significantly.
About three-quarters of cases are limb-onset ALS, meaning the first symptoms appear in the arms or legs. Early signs include muscle cramps, twitching, or a subtle weakness, often in one hand or foot. You might notice trouble gripping a pen, buttoning a shirt, or tripping more often than usual. Over time, muscles visibly shrink as the nerve connections that sustain them are lost.
The remaining cases are bulbar-onset ALS, where the disease first affects the muscles of the face, jaw, throat, and tongue. The earliest clues are slurred speech, a hoarse or strained voice, difficulty chewing, and frequent choking while eating. Bulbar-onset ALS tends to progress faster than the limb-onset form, though the pace varies considerably from person to person.
Regardless of where symptoms begin, ALS eventually spreads to other muscle groups. Limb-onset cases will develop speech and swallowing difficulties; bulbar-onset cases will develop limb weakness. The disease does not stay localized.
How ALS Is Diagnosed
There is no single blood test or scan that confirms ALS. Diagnosis is clinical, meaning neurologists piece together the picture from a physical exam, electrical tests of muscle and nerve function, imaging to rule out other conditions, and observation of how symptoms progress over time.
For decades, the standard diagnostic framework required evidence of damage in both the upper and lower motor neurons. Updated criteria, known as the Gold Coast Criteria, have broadened the definition. Patients with progressive lower motor neuron damage in at least two body regions can now qualify for an ALS diagnosis even without clear upper motor neuron signs. This change has helped some patients receive a diagnosis earlier, which matters for treatment planning and clinical trial eligibility.
Prognosis and Survival
The average life expectancy after an ALS diagnosis is three to five years. That number can be misleading, though, because the range is wide. About 30% of people live five years or more, and 10% to 20% survive at least a decade. Factors that influence survival include the site of onset (bulbar-onset cases tend to progress faster), age at diagnosis, and how quickly symptoms were spreading at the time of diagnosis.
Breathing failure is the most common cause of death in ALS. As the disease reaches the muscles that control the diaphragm, respiratory support becomes necessary, first with noninvasive ventilation and, for some patients, eventually with a ventilator.
Current Treatment Options
No therapy cures ALS, but several approved treatments can slow progression or manage specific symptoms. Riluzole, the oldest approved option, works by reducing excess glutamate that damages nerve cells. It modestly extends survival and has been available since the mid-1990s in oral form.
Radicava, approved in 2017, takes a different approach. It acts as an antioxidant, neutralizing unstable molecules called reactive oxygen species that form when cells burn energy. These molecules damage nerve cells, and by capturing them, the drug slows the loss of physical function.
For the small subset of patients with a SOD1 gene mutation, a targeted therapy called Qalsody became available in 2023. It works by blocking the production of the toxic protein that the mutated gene creates, making it the first ALS treatment designed for a specific genetic cause.
Beyond disease-modifying drugs, symptom management plays a large role in quality of life. One medication addresses pseudobulbar affect, a condition common in ALS that causes involuntary, uncontrollable episodes of laughing or crying that don’t match how the person actually feels. Physical therapy, speech therapy, nutritional support, and respiratory care are all central parts of ALS management as the disease progresses.