What is ALS? A Neurologist Explains Early Signs and a Promising New Treatment
A neurologist shares what to know about ALS, also known as Lou Gehrig’s disease, and the latest research on treatments for the disease.
Amyotrophic lateral sclerosis – commonly known as ALS – is a progressive, degenerative disease of the nervous system. In ALS, nerve cells in the brain and spinal cord deteriorate, which causes the muscles that control limb movement, speech, swallowing, and ultimately breathing to gradually weaken.
ALS is also called Lou Gehrig’s disease, named after the famous baseball player who retired because of the condition. Other notable people who had it are Stephen Hawking and more recently, the actor Eric Dane.
“In the last 20 years, we have gained considerable insight into the biology of ALS, a very complicated, multi-system disease,” says Dr. Neil A. Shneider, director of the Eleanor and Lou Gehrig ALS Center in the Department of Neurology at NewYork-Presbyterian/Columbia University Irving Medical Center. “Our research is focused on identifying new targets and strategies to treat ALS and other motor neuron diseases, giving patients the best opportunity to live longer with a high quality of life.”
Approximately 35,000 people live with ALS in the United States, with about 5,000 new diagnoses of this disease each year, according to the Centers for Disease Control and Prevention. While there’s no known cause of ALS, a recent CDC study estimates cases will rise by 10% by the year 2030.
To help understand ALS and how it is treated, Dr. Shneider, who is also the Claire Tow Professor of Motor Neuron Disorders in the Department of Neurology at Columbia University Vagelos College of Physicians and Surgeons, shared with Health Matters what the disease effects and the latest developments in cutting-edge treatments.
What is ALS?
Dr. Shneider: ALS involves two groups of motor neurons, which are nerve cells that send movement messages from the central nervous system to muscles and glands throughout the body.
The “upper” motor neurons (UMN) originate in the motor cortex and travel down the corticospinal tract that connects the brain to the spinal cord. The “lower” motor neurons (LMN) are in the brain stem and spinal cord that directly activate the muscle.
In patients with ALS, the motor neurons start to degenerate.
- When the UMN degenerates, we see exaggerated and abnormal reflexes, like the knee-jerk reflex, stiffness or spasticity, and defects in motor control.
- When the LMN degenerates, we see muscle wasting and weakness, associated with twitching and cramping.
Does ALS affect upper and lower motor neurons the same way?
Dr. Shneider: ALS patients have degeneration in both the upper and lower motor neurons—but there is a spectrum. The degree to which the upper and lower neurons are affected varies considerably from person to person, and this variation can heavily affect how the disease presents and progresses.
Do we know what causes ALS?
Dr. Shneider: Unfortunately, in most cases we do not. In about 90% of ALS cases there is no family history of the disease — this is called sporadic ALS. Approximately 10% to 15% of people with ALS carry a genetic variant that causes the disease, and this is called familial ALS.
Some studies suggest the following factors raise ALS risk:
- Genetics. A family history of ALS — or the presence of a spontaneous (or de novo) variant - increases the chance that someone may develop the disease.
- Age. While ALS can affect anyone of any age, symptoms commonly begin between 50 and 70.
- Gender. Men are slightly more likely than women to develop ALS, but this difference diminishes with older age.
- Race and ethnicity. Non-Hispanic white individuals are more likely to develop ALS.
- Military service. Research suggests that military veterans are about 1.5 to 2 times more likely to develop ALS. Although the reason for this is unclear, possible risk factors for veterans include exposure to lead, pesticides, and other environmental toxins.
How is ALS diagnosed?
Dr. Shneider: There are a variety of approaches to test for and diagnose ALS, which may include:
- Physical and neurological examination to evaluate symptoms.
- Blood and urine tests to rule out the presence of other diseases that may cause similar symptoms.
- Electrodiagnostic tests (such as electromyography and nerve conduction studies) which evaluate muscle and nerve function.
- Muscle and/or nerve biopsy to determine if another muscle disease may be causing the symptoms.
- Imaging tests such as magnetic resonance imaging (MRI) to visualize the brain and spinal cord.
- Understanding of family and personal medical history.
- Genetic counseling and testing for known pathogenic variants in ALS genes.
What are the signs and symptoms of ALS?
Dr. Shneider: ALS can begin in many different ways, and no two patients experience the disease in the same way. In "limb onset" ALS, people first notice weakness or wasting in a hand, arm, or leg. Others develop early problems with speaking or swallowing, referred to as "bulbar onset" disease. In rare cases, breathing difficulties are the first sign.
The age at which symptoms begin varies widely, ranging from the pre-teens to the eighties, though most people are diagnosed between the ages of 50 and 70.
Once symptoms begin, the disease typically progresses, but the pace varies considerably — some people decline rapidly and survive only a year or two after diagnosis, while others progress more slowly and live for a decade or longer. However, most people with ALS survive two to five years from the time symptoms first appear.
This broad variability in where the disease starts, how fast it moves, and how long patients live makes ALS a challenging disease to study, to treat, and to predict, which underscores the need for better tools to understand what drives these differences from one patient to the next.
Early ALS symptoms
- Muscle twitches and stiffness
- Loss of control of the hands and arms
- Weakness
- Fatigue
- Tripping and falling
- Dropping objects
- Slurred speech
Advanced ALS symptoms
- Challenges with movement
- Difficulty swallowing
- Labored speech
- Difficulty breathing
- Paralysis
Cutting-edge ALS Therapy
Dr. Shneider is currently leading a global phase 3 clinical trial of an experimental drug called ulefnersen (originally named jacifusen) in ALS patients who carry a mutation in the FUsed in Sarcoma (FUS) gene. FUS-ALS is a particularly aggressive form of the disease, often associated with pediatric and juvenile onset and rapid progression. This new trial is based on promising results from a study at Columbia published in the January 24, 2022 issue of Nature Medicine that demonstrated that ulefnersen not only safely lowered levels of the toxic FUS protein in an animal model of FUS-ALS, but in a first in human study, it also lowered levels of FUS in a young woman named Jaci Hermstad, whose story you can read about here.
“This trial will determine if the drug is safe, and if it can effectively slow disease progression in symptomatic FUS-ALS patients,” Dr. Shneider says. “If approved, it would be the first treatment for this highly aggressive form of early-onset ALS.”
Does ALS only impact movement and muscle control?
Dr. Shneider: No. ALS is increasingly recognized as a disease that can affect cognition and behavior, not just movement. Estimates suggest that roughly 50% of people with ALS experience some degree of cognitive or behavioral change during the course of their illness. Approximately 15% of ALS patients are diagnosed with frontotemporal dementia, or FTD, a condition characterized by marked changes in personality and behavior or significant language impairment.
The cognitive changes are linked to involvement of the frontal and temporal lobes of the brain, the regions responsible for decision-making, personality, language, and social behavior. At the milder end of the spectrum, patients may notice subtle difficulties with attention, word-finding, or emotional regulation that do not significantly interfere with daily life.
ALS and FTD are now understood to be part of a biological continuum — linked by shared genetic causes and by the same abnormal protein accumulations found in the neurons of most patients with either disease.
The recognition that ALS is not purely a motor disorder has important implications for how patients are cared for, how clinical trials are designed, and how we think about the underlying biology driving neurodegeneration across both conditions.
How is ALS treated?
Dr. Shneider: There is no way to reverse the motor neuron damage of ALS or to cure the disease. However, there are treatments available to control ALS symptoms and make living with the disease easier:
Medications
Several drugs for ALS are being assessed in clinical trials, but only two drugs — riluzole (Rilutek®) and edaravone (Radicava®) — are currently approved by the FDA for treating ALS. Other medications may be used to alleviate symptoms such as muscle cramps, stiffness, and excess saliva.
Nutritional support
Dietitians can design an eating plan of small meals that provide sufficient nutrients while avoiding foods that may be challenging to swallow. ALS patients should eat foods high in antioxidants and carotenes, such as fruits and vegetables, along with foods high in fiber, such as grains, fish, and lean protein. In the later stages of the disease, patients may require the placement of a feeding tube.
Rehabilitation
Physical, occupational, speech and swallowing, and respiratory therapy help ALS patients maintain their strength and function as long as possible. Special equipment can help patients continue to communicate effectively, remain mobile, and ensure their safety.
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