In this blog post, we’ll examine the definition, symptoms, causes, and treatments of amyotrophic lateral sclerosis (ALS)—commonly known as Lou Gehrig’s disease—and explore what has been discovered to date.
When people hear terms like “incurable disease,” “intractable disease,” or “rare disease,” the number of illnesses that come to mind is likely very limited. Even I, who dreamed of becoming a doctor and enrolled in medical school, could only think of three or four conditions—including cancer, a disease everyone knows. However, thanks to the “Ice Bucket Challenge” campaign—which spread globally via social media—there is one disease name that has remained etched in the memories of countless people: “Lou Gehrig’s disease.”
ALS, short for Amyotrophic Lateral Sclerosis, is known in Korean as “muscle-wasting lateral sclerosis.” Also known as “Lou Gehrig’s disease” after the baseball player Lou Gehrig—who, alongside Babe Ruth, led the New York Yankees to their golden age—this disease is a progressive neurodegenerative disorder in which the motor neurons in the brain and spinal cord gradually deteriorate and die, leading to muscle weakness. Looking at the term “Amyotrophic Lateral Sclerosis,” “a” means “without,” “myo” means “muscle,” “trophic” means “nutrition” or “nutritional status,” “lateral” refers to the lateral side of the spinal cord, and “sclerosis” means “hardening.” Putting this together, we can infer that it is a disease in which muscles gradually weaken and atrophy due to damage to motor neurons.
The human nervous system can be broadly divided into the central nervous system, which includes the brain and spinal cord, and the peripheral nervous system, which includes motor and sensory nerves. The roles of each can be inferred to some extent from the types and names of the nerves they contain. Lou Gehrig’s disease is characterized by the selective damage to motor neurons among these various nerve types, and both upper and lower motor neurons can be affected. Upper motor neurons transmit commands from the brain to the spinal cord, while lower motor neurons transmit commands from the spinal cord to the muscles. Damage to upper motor neurons can lead to symptoms such as muscle rigidity and hyperreflexia, whereas damage to lower motor neurons can result in muscle weakness, atrophy, or muscle spasms. Since both types of motor neurons can be affected in ALS, symptoms such as stiffness, muscle weakness, and muscle atrophy often occur together. However, while it was previously often explained that only the motor system was selectively damaged—with no issues affecting sensation or cognitive function—it is now known that some patients may experience cognitive impairment or behavioral changes, and that frontotemporal dementia may also occur concurrently.
One might think that simply having weak muscles isn’t a major problem. However, muscles aren’t used solely for walking or moving the arms. When muscles weaken, not only is movement restricted, but speaking can also become difficult. Since the muscles needed for chewing and swallowing also weaken, it becomes difficult to eat properly; furthermore, if the muscles involved in breathing weaken, respiratory function may decline. Therefore, as the disease progresses, respiratory support treatments—such as non-invasive mechanical ventilation—may be administered while continuously monitoring respiratory status, and in cases of severe respiratory failure, invasive mechanical ventilation via tracheostomy may be considered. Furthermore, since swallowing difficulties increase the risk of aspiration pneumonia or malnutrition, nutritional management and airway protection are also crucial. Although the course of ALS varies greatly from patient to patient, the average survival period after the initial onset of symptoms is generally known to be about 3 to 5 years. However, some patients survive much longer than this, and there are even cases, such as that of Stephen Hawking, who lived with the disease for decades.
So, what causes this disease? Unfortunately, the exact cause of all cases of ALS has not yet been identified. About 10% of all patients are classified as having familial ALS, while the majority of the remainder have sporadic ALS, which occurs without a clear family history. That said, ALS-related genetic mutations can be found even in patients without a family history, and to date, it has been suggested that various genes and environmental factors may contribute to the risk of developing the disease. In the past, hypotheses regarding various causes—including specific dietary and environmental factors in Guam—were proposed, but it is difficult to explain the majority of ALS cases with just one specific factor. ALS occurs worldwide, and U.S. data report an annual incidence rate of approximately 2 cases per 100,000 people. In South Korea, according to data from the National Health Insurance Service cited by Asan Medical Center in Seoul, the annual incidence rate is reported to be 1.2 cases per 100,000 people, the prevalence rate is 3.43 cases per 100,000 people, and the average age at diagnosis is 61.4 years. Since the figure of approximately 1,500 patients in South Korea mentioned in the original text is unlikely to reflect current data, it is more appropriate to refer to these latest incidence and prevalence figures rather than using the older number as is.
Not only has the exact cause not been fully identified, but to date, no cure for all forms of ALS has been developed. However, unlike in the past, various treatments are now available that help slow the progression of symptoms, prolong survival, and improve quality of life. Representative medications include riluzole and edaravone. Riluzole is known to influence neuroexcitotoxic processes, including those involving glutamate, thereby providing certain benefits in terms of disease progression and survival. Edaravone may help slow functional decline in some patients by reducing oxidative stress; in the United States, it is approved not only as an intravenous injection but also as an oral suspension. Furthermore, while not applicable to all ALS patients, a targeted therapy called tofersen can be used for adult patients with a confirmed SOD1 gene mutation. Tofersen is a treatment designed to reduce the production of the SOD1 protein and received approval from the U.S. Food and Drug Administration (FDA) in 2023. Therefore, current ALS treatment goes beyond simply extending life expectancy; it takes a multifaceted approach that combines drug therapy to slow disease progression with the management of functions such as breathing, nutrition, swallowing, and communication. However, we have not yet reached the stage where damaged motor neurons can be fully restored or the disease can be fundamentally cured for all patients, and research to develop more effective treatments continues.
Although this article is brief, we have taken a brief look at the definition, symptoms, causes, and treatments of ALS. In the past, the “Ice Bucket Challenge” significantly increased public awareness of ALS and expanded research funding, and even now, various institutions and researchers are conducting studies to develop new treatments. In particular, with the recent emergence of treatments that target specific genetic mutations, ALS research is evolving from a one-size-fits-all approach toward a precision medicine approach tailored to each patient’s genetic characteristics and the underlying causes of the disease. Although a cure for ALS does not yet exist, we hope that these advancements in research and treatment will someday provide more effective therapies and new hope to patients suffering from ALS.
