ALS Overview

Written by Margaret Anne Rockwood | Last updated April 29th, 2026
Medically reviewed by Doreen Ho, MD and Jennifer Morganroth, MD, MBA

ALS Incidence Rises, but Causes Remain Poorly Understood

About 33,000 people in the U.S. today are living with Amyotrophic Lateral Sclerosis (ALS). Clinicians suspecting or confirming an ALS diagnosis find themselves in an increasingly common position in the medical world today. They must tell their patient and families that an individual has a disease of progressive disability, likely to take their lives on average within 2 to 5 years, and for which there is not yet a curative treatment.

Still, knowledge is power, for the clinician and patient. Increasingly, we have therapies to help attenuate symptoms, slow progression and provide assistive devices to help mitigate the impact of lost function. Importantly, with the pace of advancements in gene and gene modifying therapies, stem cell therapy and high-throughput drug screening clinicians may soon be able to offer further hope to their patients.

Epidemiology

ALS is a progressive neurodegenerative disorder characterized by loss of upper motor neurons (UMN) in the motor cortex and lower motor neurons (LMN) in the brainstem and spinal column.

About 10-15% of cases are related to known genetic causes, with the other 85-90% arising from a confluence of poorly understood triggers and complex mechanisms of action. Ultimately, biochemical anomalies overwhelm the normal resiliency of motor neurons until they become undernourished and fail to transmit signals to stimulate muscle activity.

Prevalence

Today, the prevalence of ALS in the U.S. is approximately 7.7 per 100,000 people, but with an aging population and the accompanying aggregation of environmental insults, the current upward trend is predicted to steepen. Globally, the estimated number of ALS cases are estimated to increase ~69% between 2015 and 2040, in part due to an aging population. While the incidence is fairly constant among same-age people over 70, age those 40-70 have risen.

Age of Onset and Survival

The mean age of onset is 58–63 years for sporadic ALS and 40–60 years for familial ALS, with a peak incidence in those aged 70–79 years old. Juvenile ALS (<25 years) is extremely rare and about 40% have pathogenic mutations in known ALS-associated genes.

The median survival from symptom onset is 2-5 years, with 20-30% living 5 years and 10-20% living 10 years.

Sex Differences

There is a slight male predominance (roughly 1.2:1 to 1.5:1), particularly for limb-onset ALS. This gap narrows significantly in post-menopausal cohorts, suggesting a potential neuroprotective role of estrogen or other hormones.

Ethnicity

Current data suggests that ALS incidence is highest in non-Hispanic white populations and lower in Hispanic, African, and Asian populations.

Who is most vulnerable to developing ALS?

Genetic, or familial, ALS is understood to be driven by inherited autosomal dominant (and, rarely, autosomal recessive) pathogenic variants, usually in C9orf72, SOD1, and TDP-43+FUS genes. About 15% percent of people living with ALS have a familial origin.

If one parent has one of these pathogenic variants, the odds of their offspring inheriting the gene are 50-50. However, because of incomplete penetrance, only 19-54% of those who inherit the mutation develop ALS. Ranges vary by gene.

Other pathogenic variants (heritable or de novo) are increasingly implicated as playing a role in ALS. As a result, the current ratio of genetic to sporadic ALS may shift as new genes are identified as causal or otherwise significant in disease development. This, combined with our growing understanding of the roles epigenetics play in disease, is driving more discoveries about the genetic environment underpinning ALS.

Sporadic ALS develops without known genetic roots. Associations have been found with several  environmental and lifestyle factors, and may play a role in the development of ALS:

• Military Service
• Smoking
• Occupational and environmental toxins (e.g., heavy metals, pesticides, cyanobacteria)
• Intense physical or traumatic histories

However, the relative risk associated with these factors appears to be small to moderate, and no one factor accounts for more than a minority of cases.

In short, sporadic ALS almost always reflects a multifactorial interplay of age, genetics, and environment, rather than a single identifiable cause.​

Populations with the longest survival

Age shows the highest association with the disease, over and above environmental and lifestyle factors. Features of longer survivors include those who are younger at age of onset, those who experience limb (vs bulbar) symptoms at onset, who have slower progression and preserved respiratory function at presentation, and who receive early multidisciplinary care. Conversely, bulbar onset, rapid early decline, and significant respiratory compromise predict shorter survival.​

What clinicians can do to support patients following diagnosis of ALS

Differential diagnosis in neurodegenerative and neuromuscular diseases is complex, and some ALS symptoms can be particularly misleading. It is important to fully grasp the advantage of an early diagnosis, as the opportunity to significantly slow disease progression is at stake.

For symptomatic patients with and without family histories, offering genetic counseling and testing is appropriate, particularly when results might guide trial eligibility or gene-targeted therapy.​

ALS is still a rare diagnosis in primary care practices. With the benefits of early treatment in mind, helping navigate patients to prompt evaluation by neurologists or subspecialists may be challenging.

Rising rates of diagnoses have clinical implications for the capacity to treat and to provide ventilatory and nutritional support services and palliative care planning.​ For neurologists and subspecialists who have confirmed an ALS diagnosis, tapping into a reliable bank of resources that includes social workers; mental health counselors; psychiatrists; nutritionists; occupational, physical, and speech and language therapists, has a proven impact on survival and quality of life.

Selecting appropriate clinical trials for patients to consider is a large part of the clinical relationship. According to one U.S. survey, a majority of patients were eager to participate, but relatively few knew where to access trial information. Early referral to an ALS clinic that may help patients enroll in trials is important for helping interested patients find trials. Partnership between patients and scientific community is critical.

When offered the option, half or more of people living with ALS may donate their brain or spinal cord to further scientific research.

Disease-Modifying Therapies and the Search for Cure

Recent advancements in ALS research may reshape how clinicians understand and help patients manage the disease. New drugs that inhibit excitability factors and target various sites along newly-elucidated disease pathways are emerging on an ongoing basis.

Nascent stem cell, gene-therapy (includingCRISPR-Cas9 manipulations) and immunotherapy appear ripe for breakthrough treatments that target both genes and cellular pathways.

Neuromodulation, brain-chip interfaces and exoskeletons are offering life-changing supports so more patients can ambulate and communicate.

Hope for accelerated treatment solutions rests on a continued strong momentum behind research, patient engagement, cross-learning among researchers in other neurodegenerative disease studies, the increasing interest we are seeing in the field, as well as the critical impact of patient advocacy in driving and funding innovation.

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