Understanding Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's Disease

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease after the legendary baseball player, is a progressive neurodegenerative disorder that impacts thousands of individuals in the United States each year. This complex disease primarily targets motor neurons—the nerve cells responsible for voluntary muscle movements—leading to their degeneration and death. Consequently, the transmission of signals from the brain to muscles is disrupted, resulting in muscle atrophy, weakness, and paralysis, eventually impairing vital functions like breathing.

Most individuals diagnosed with ALS experience a gradual decline in mobility, speech, eating, and respiratory function, though their cognitive abilities typically remain intact. The disease progression varies widely among patients, with survival time post-diagnosis generally ranging from two to five years. Despite its variability, ongoing research and emerging treatments offer hope for improved quality of life and increased survival rates.

May marks ALS Awareness Month, spotlighting the importance of understanding this disease—its impact, progression, and the advances in research, care, and support for affected families.

What is ALS?

ALS is primarily characterized by the deterioration of motor neurons located in the brain and spinal cord. These neurons control voluntary muscles, and their loss leads to muscle weakness, atrophy, and loss of motor function. As the disease advances, individuals may experience difficulty walking, speaking, swallowing, and breathing. Importantly, most patients retain their cognitive functions, though some may develop behavioral or cognitive changes, including frontotemporal dementia.

Who is affected by ALS?

Anyone can develop ALS, but most cases are diagnosed between ages 40 and 70. In the U.S., approximately 5,000 new cases are diagnosed annually, with around 30,000 people living with the disease at any given time. About 90% of cases are sporadic, occurring with no family history, though genetic factors are increasingly recognized. The remaining 10% to 15% of cases are familial, inherited through genetic mutations.

Certain groups, such as military veterans, are at higher risk, possibly due to environmental exposures or physical injuries. Firefighters may also have elevated risk due to exposure to toxins and smoke. Recognizing these risk factors underscores the need for ongoing research into environmental and occupational contributors, as well as accessible specialized care, especially for at-risk populations.

What are the symptoms?

Early symptoms of ALS can be subtle and vary, often beginning with muscle cramps, twitching, or stiffness in a limb or speech difficulties. As the disease progresses, these symptoms expand to involve widespread muscle wasting, weakness, and difficulty with fine motor tasks. Bulbar symptoms include speech and swallowing problems, tongue atrophy, and drooling.

Respiratory issues become more prominent as motor neurons controlling breathing muscles deteriorate, leading to breathing difficulties, shortness of breath, and irregular breathing patterns. Additionally, up to half of ALS patients experience cognitive or behavioral changes, with some developing frontotemporal dementia.

Causes and Risk Factors

The exact cause of ALS remains unknown, though genetics play a significant role. Researchers have identified nearly 50 genes linked to ALS, with mutations in SOD1, C9orf72, TARDBP, and FUS being most common. In sporadic cases, a combination of genetic susceptibility and environmental factors—such as toxin exposure, heavy metals, viral infections, physical trauma, or intense physical activity—may contribute.

Diagnosis

Diagnosing ALS is complex, involving clinical assessments, genetic testing, electromyography (EMG), nerve conduction studies, and brain imaging to exclude other neurological conditions. Early and accurate diagnosis is vital for access to therapies, clinical trial participation, and comprehensive care.

Treatment Options

While there is currently no cure, several FDA-approved therapies can slow disease progression. Riluzole reduces nerve cell excitability; Edaravone acts as an antioxidant to slow nerve damage; and Tofersen offers targeted treatment for specific genetic mutations. Ongoing clinical trials aim to discover new treatments, with over 120 active studies worldwide and innovative approaches like gene therapy, biomarkers, and AI-driven diagnostics driving progress.

Research and Future Directions

Current research focuses on RNA-targeted therapies, gene editing, biomarkers for early detection, and leveraging artificial intelligence to personalize treatments. Collaborative efforts such as the AMP ALS and ALL ALS initiatives aim to accelerate discovery and improve clinical trial efficiency, bringing new hope for future breakthroughs.

Living with ALS

Many individuals diagnosed with ALS maintain active and meaningful lives through supportive interventions, assistive technologies, and multidisciplinary care. Organizations like the Muscular Dystrophy Association provide vital resources, research funding, and comprehensive care centers to support those affected.

The Path Forward

Despite its devastating nature, progress in understanding and treating ALS continues. With sustained research efforts and community support, the goal is to develop more effective therapies, enable earlier diagnosis, and ultimately find a cure for this challenging disease.

Source: https://medicalxpress.com/news/2025-05-als-lou-gehrig-disease.html