Every 90 minutes someone is diagnosed with amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative
disease that causes muscle weakness, paralysis, and ultimately, respiratory failure.
ALS, also known as Lou Gehrig’s disease, Charcot's disease, and
motor neuron disease (MND),
attacks certain cells in the brain and spinal cord needed to keep our muscles moving. Early signs and symptoms
of ALS include:
- muscle cramps and muscle twitching
- weakness in hands, legs, feet or ankles
- difficulty speaking or swallowing
The senses, including hearing, sight, smell, taste, and touch, are not affected by ALS.
There is no single diagnostic test for ALS. However, experts in the disease, usually neurologists specializing in
neuromuscular diseases, are very capable of diagnosing
ALS. In some cases, they might order additional tests if the diagnosis is not clear. These include:
Most people with ALS live 2-5 years after their first signs of disease. About 10% of people with ALS survive at
least 10 years. This variable rate of disease progression makes
difficult to predict and therapies challenging to develop.
Currently, there is only a single medicine for specifically treating ALS -
riluzole. The drug, marketed by
Sanofi-Aventis under the name Rilutek, extends survival by only about 2 to 3 months.
This urgent unmet medical need for effective
for this devastating and fatal disease is the basis for the research and drug development effort at the
nonprofit biotech organization, ALS Therapy Development Institute.
In people with ALS, the motor neurons
deteriorate leading to muscle weakness and paralysis. Why these cells are particularly vulnerable remains an open
question, but scientists are beginning to unravel how these cells are destroyed, leading to new ways to attack the
Many cells in the nervous system contribute to ALS.
Courtesy of Stanford University School of Medicine
When neurologist Jean-Martin Charcot, MD, first peered into the tissues of his patients lost to ALS in 1865,
he noticed clear signs of progressive neuronal damage that stretched from the brain to the brain stem
(upper motor neurons) to the spinal cord
(lower motor neurons) and
atrophy of neighboring muscles.
Scientists now understand that this neurodegeneration is extremely complicated and occurs through several mechanisms.
Misfolded proteins accumulate. Sodium channels act up
Epigenetic and genetic switches are thrown.
Energy-producing mitochondria malfunction, leading
to a power drop. Free radicals build up, increasing
oxidative stress. Toxic substances
All of these mechanisms appear to contribute to motor neuron destruction in ALS. Many more are suspected to play
a key role in the onset and progression of the disease.
Since the 1980s, scientists have recognized that ALS is
much more than a motor neuron disease.
microglia entrusted to keep motor neurons healthy
and free from infection
producing toxic substances that damage them, fuel the progression of ALS.
Macrophages and certain
T-cells infiltrate the
nervous system potentially unleashing a storm of cytokines of their own that further contributes to the disease.
Oligodendrocytes appear to
lose their ability
to power motor neurons up in people with ALS,
contributing to the energy drain
and their destruction.
Tools such as electromyography (EMG) are used in the
diagnosis process. Courtesy of Royal North Shore
There is no single diagnostic tool for ALS. A series of clinical procedures are conducted to rule out neurological
conditions whose symptoms closely resemble the disease. In the US, the diagnosis can take about 12 to 14
months. Researchers hope to expedite this process by developing tools that indicate whether
people have the disease.
In people with ALS, motor neurons degenerate and become unplugged from neighboring muscles resulting in muscle
weakness and muscle atrophy. Some neurological diseases,
share the same conditions, to distinguish them, clinicians run tests which can include:
Electromyography (EMG) and nerve conduction studies (NCS)
These tests enable clinicians to check whether motor nerves are plugged into the muscles and are working
properly. NCS tests whether the motor nerves can send signals of sufficient strength to enable movement of the
muscles. EMG measures the abilities of these muscles in response to these signals to trigger contraction.
These tests help rule out certain disorders including those of the peripheral nerves.
Clinicians may also recommend a biopsy to further investigate affected muscles. Examination of muscle tissue
under the microscope can help rule out certain muscle diseases.
Magnetic Resonance Imaging (MRI)
MRI enables clinicians to peer into our organs and our tissues including the brain and spinal cord. MRI can help
rule out a number of conditions including brain tumors,
multiple sclerosis and certain disorders of
the spinal cord.
Most cases of ALS are sporadic (sALS) in nature. About 10% of cases, however, are inherited. When a
familial case of ALS (fALS) is suspected, genetic
testing might also be recommended. Commercially available tests can identify alterations in 9 ALS-linked genes.
Other tests include blood and urine tests and spinal tap.
During this process, people with ALS might receive a diagnosis of suspected,
probable ALS. These designations depend on which parts of
the body are affected by the disease.
Without a definite diagnosis, people with possible or
probable ALS nevertheless remain
eligible to participate in a
growing number of clinical trials evaluating emerging
for the disease. Check out our clinical trials page.
A growing number of researchers suspect that
MRI might help to do much more than exclude
other diseases. Certain brain scans might
indicate whether a person has ALS. Researchers hope these signatures called
biomarkers can be used to identify people who are at high
risk of developing fALS before they
develop the disease.
Meanwhile, other scientists are developing a new method called electrical impedance myography (EIM) to diagnose ALS.
This test helps identify key changes in affected muscles including atrophy. Scientists hope that this tool might
also predict the spread of ALS and help them to develop treatments for the disease.
A spirometer measures lung function and is used to monitor
changes in a PALS functional abilities
Most people with ALS live about 2-5 years after experiencing their first signs of the disease. At least 1 in 10
people live more than 10 years following their diagnosis. This variable rate of progression makes predicting
prognosis difficult. Clinicians instead rely on regular follow-up visits to monitor people with ALS to
manage their disease.
Early signs of ALS
Most people with ALS first feel muscle cramps, spasms or twitching
(fasciculations) in one of their arms or legs.
Other signs include weakness in the hands and feet or loss of balance. This form of the disease is called
About 25% of people with ALS first have trouble talking clearly - slurring words. This form of the disease is
called bulbar-onset ALS.
After receiving a diagnosis,
people with ALS typically attend regular clinic visits about every 3-4 months. During these visits, each patient is monitored
for changes in their functional abilities. Commonly used tests include:
ALS Functional Rating Scale-Revised (ALSFRS-R):
A rating scale that measure changes including breathing, speaking, sleeping, swallowing, and walking. The score
is based on answers to 12 questions using a 48-point scale.
Spirometry: A test that measures lung
function. Breathing abilities are typically estimated based on the maximum amount of air that can be blown out
either slowly (slow vital capacity - SVC) or quickly
(slow vital capacity - SVC).
Middle stages of ALS
As the disease spreads, many muscles weaken and start to stiffen. Range of motion exercises will likely be recommended to help
keep muscles loose and prevent the formation of contractures and
People with ALS might tire more easily. Breathing may be affected. A BiPAP machine or a
phrenic pacer might be suggested, particularly to help improve
sleeping. A feeding tube might be suggested to help meet nutritional needs. Medications might be also recommended to
control emotions (pseudobulbar affect) or reduce muscle spasms.
People with bulbar-onset often work with a speech therapist to keep talking longer. People with limb-onset ALS may
rely on a cane, walker, or wheelchair due to difficulties walking and maintaining balance.
Late stages of ALS
As the disease progresses, muscles become paralyzed. Most people with ALS require a wheelchair to get around and may
communicate through assistive devices using an eye-tracking device or a letter board.
People with late-stage ALS are often cared for in hospices or at home. Some people with ALS choose invasive ventilation
to help keep them breathing. Most people lose the battle with ALS due to respiratory failure.
There is no cure or effective treatment for ALS, however scientists are working hard to develop therapies for
ALS is a complex multi-system disease. A growing number of ALS clinics are deploying multidisciplinary
teams to care for people with ALS to meet their physical, emotional, and nutritional needs. These teams
include physical, respiratory, speech and occupational therapists to help people with ALS breathe easier,
keep moving, and stay connected. Palliative care specialists support people with ALS and their caregivers.
Today, there are dozens of clinical trials evaluating potential treatments enrolling people with ALS and
their families. Check out our clinical trials page.
Researchers are developing a number of treatment strategies to fight ALS. GSK's
ozanezumab hopes to keep ALS in check by protecting the
neuromuscular junctions from crumbling.
Immune system-modulating drugs including Neuraltus Pharmaceuticals'
NP001 hope to slow ALS in its
tracks by reducing neuroinflammation.
Stem cell-based strategies including
Neuralstem's NSI-566 and Brainstorm's
hope to shield
motor neurons from destruction. And, potential muscle boosters
hope to help
people breathe easier and keep muscles moving.
Scientists are also repurposing medicines in hopes of bringing ALS therapies more quickly to the clinic. The
FDA-approved heart medicine
mexiletine might slow ALS by
reducing hyperexcitability, a potentially early step in the disease. The multiple sclerosis medicine,
Novartis' Gilenya, aims to
treat ALS by reducing neuroinflammation.
The DPS might improve the QoL of people
with ALS and extend survival.
There are also a growing number of medicines that might help alleviate key symptoms of the disease. Baclofen may reduce
muscle spasms. Nuedexta might
help keep emotions in check (pseudobulbar affect).
might reduce painful muscle cramps. A number of medicines
including Robinul, Elavil, and Botox, may help reduce salivation.
Care and management
Breathing devices may also improve quality of life and extend survival.
Non-invasive ventilators such as a BiPAP machine
help people with ALS breathe better, sleep better and boost survival by about a year according to some estimates.
Phrenic pacers (NeuRX DPS) might also help people
sleep better and extend survival
according to clinical observations
about 16 months after NIV use is initiated.
Clinical trials are
ongoing to further evaluate
the NeuRX DPS and identify which people with ALS might benefit from them.
Certain forms of exercise are also becoming routine. Range of motion (stretching) is general practice for people with
ALS to prevent muscle pain and the formation of contractures.
Emerging aerobic workouts
might improve quality of life and help reduce functional decline. A clinical trial
evaluating the benefits of certain forms of exercises including stationary cycling and weight training remains ongoing.
There is no cure or effective treatment for ALS. This urgent unmet medical need for effective ALS therapies is
the basis for the research and drug development effort at the nonprofit biotech organization,
ALS Therapy Development Institute.