ALS Overview
Amyotrophic lateral sclerosis (ALS), also known as Motor Neuron Disease (MND), Lou Gehrig's Disease,
and Charcot's disease, is a progressive neurodegenerative disease that attacks motor neurons in the
brain and spinal cord. This results in the wasting away of muscle, loss of movement, and eventual
paralysis.
Roughly 1 in 400 people will develop ALS in their lifetime, and there are an estimated 30,000 people
living with ALS in the U.S. at any given time. We are still learning much about what causes ALS. About
85% of all ALS cases are sporadic with no known history of the disease in a family. The remaining 15%
of cases of ALS are familial (inherited) ALS. ALS affects people of all races, ages, and genders.
Video: What is ALS?
There are currently no treatments to stop or reverse ALS progression, but researchers at the
ALS Therapy Development Institute (ALS TDI) and around the world are working to change this.
The first symptoms of ALS can vary, but early signs and symptoms may include:
- muscle cramps and muscle twitching
- weakness in hands, legs, feet or ankles
- difficulty speaking or swallowing
These symptoms will continue to progress, eventually causing paralysis. The senses, including hearing,
sight, smell, taste, and touch, are not affected by ALS. In most cases of ALS, memory and thinking are not affected.
ALS is not experienced in the same way among all those diagnosed. The manner and speed at which the disease
moves throughout a person's body can vary greatly.
Most people live about 3-5 years after experiencing
their ALS symptoms, with one in ten people surviving for at least 10 years. The variable rate of disease
progression makes
prognosis difficult to predict and therapies
challenging to develop.
Currently, there are no effective cures or treatments to stop ALS disease progression. ALS is a
complex disease that varies from person to person. Far more research is necessary to discover effective
treatments for each person living with ALS. That's why researchers at the ALS Therapy Development Institute
(
ALS TDI) are working hard each day to find ALS treatments. We aim to do this by identifying,
testing, and developing promising new treatments and learning more about ALS through our ALS Research Collaborative
(
ARC).
What causes ALS?
Amyotrophic lateral sclerosis, ALS, is caused by progressive deterioration and death of motor neurons,
leading to muscle weakness and paralysis.
Fifteen percent of cases are known as
familial ALS, in which a specific genetic mutation is
inherited and passed down from generation to generation. Over 40 ALS-related genes
have now been identified
[1]. The most
common known genetic mutation in ALS is the C9orf72 gene, which accounts for approximately 30
to 40 percent of all familial ALS cases
[1].
Mutations in the SOD1 gene make up around 20 percent of familial ALS, and TARDBP and FUS gene
mutations each account for about 5 percent of familial cases.
The remaining 85 percent of cases are known as
sporadic ALS, meaning there is no known
history of the disease in a family. There are many theories outlining potential causes of ALS
including oxidative stress, mitochondrial dysfunction, immune system over activity, glutamate
toxicity and toxic exposures. Studies have shown that those who have served in the military
are more likely to develop ALS than the general population
[2],
[3].
It is important to note that clinically, familial ALS and sporadic ALS appear to be
indistinguishable from one another.
ALS can affect anyone of any age, gender or race.
However, for the most part, ALS affects people between the
ages of 40 and 70. ALS appears to affect men at a
higher rate than women below the age of 65. Over the age of 70, ALS evidence has shown that ALS affects men and
women at the same rate. According to recent research, ALS appears to be more common in white populations than in
African American, Asian, or Hispanic populations
[4] [5].
Diagnosis
There is no single diagnostic tool for ALS. The El Escorial criteria is commonly used to aid diagnosis, which requires the following:
- Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination.
- Evidence of upper motor neuron (UMN) degeneration by clinical examination.
- Progressive spread of symptoms or signs within a region or to other regions, as determined by history or examination.
A series of clinical procedures may also be conducted to rule out neurological conditions whose
symptoms closely resemble ALS. This means the ALS diagnostic process includes eliminating the
possibility of many other diseases, including infections like Lyme disease and other neurological
disorders such as multifocal motor neuropathy, before making a final diagnosis. For this reason,
diagnosis can take as long as 12 to 14 months.
Throughout the diagnostic process, people may receive a diagnosis of
suspected, possible, probable, or definite
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 treatments for the disease. For a full list
of ALS studies, visit our
clinical trials page.
Some of the procedures a person may undergo on their way to an ALS diagnosis may include:
-
Genetic testing: When a familial case of ALS
(fALS) is suspected, genetic testing might also be recommended. Commercially available tests can identify dozens
of ALS-related genes. People that undergo genetic testing are typically provided genetic counseling, during which
they learn how to interpret results.
-
Electromyography and nerve conduction studies: These tests enable clinicians to determine whether motor
nerves are plugged into the muscles and are working properly. Nerve conduction studies (NCS) test whether
the motor nerves can send signals of sufficient strength to enable movement of the muscles.
Electromyography (EMG)
tests measure the ability of these muscles to trigger contraction in response to these signals. These
tests help rule out certain other disorders that resemble the early symptoms of ALS.
-
Muscle Biopsy: Clinicians may also recommend a biopsy to further investigate affected muscles. Examination
of muscle tissue under a microscope can help rule out certain muscle diseases.
-
Magnetic Resonance Imaging (MRI): MRI enables clinicians to examine organs and tissues including
the brain and spinal cord. An MRI can help rule out a number of conditions including brain tumors,
multiple sclerosis, and
certain disorders of the spinal cord.
-
Other tests: These include blood, urine tests, and spinal taps. However, researchers hope to expedite the diagnostic process by developing tools that directly indicate whether a person has the disease.
Emerging tools
A growing number of researchers suspect that
MRI could
indicate whether a person has ALS rather than just eliminate other diseases. Researchers hope certain
biomarkers can be used to identify people
who are at high risk of developing ALS
before they show symptoms.
Meanwhile, other scientists are developing a new method called electrical impedance myography (EIM) to
diagnose ALS. This test helps identify changes in affected muscles, including atrophy. Scientists hope
that this tool might also predict the spread of ALS and aid in the development of treatments for the disease.
Prognosis
Most people with ALS
have a life expectancy of about 3-5 years after experiencing their first ALS
Symptoms. At least one in ten 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.
Most people's early ALS symptoms include
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 limb-onset ALS.
About 25 percent of people with ALS first have trouble talking clearly and begin to experience
slurred speech. This form of the disease is called bulbar-onset ALS.
After receiving a
diagnosis, people
with ALS often schedule regular clinic visits every 3-4 months. During these visits, patients are monitored
for changes in their functional abilities and ALS symptoms.
Commonly used tests for monitoring ALS include:
-
Spirometry: This is 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 (forced vital capacity - FVC).
-
ALS Functional Rating Scale-Revised (ALSFRS-R): The ALSFRS-R is a questionnaire that measures
changes in a person's abilities, including breathing, speaking, sleeping, swallowing, and walking. The
score is based on answers to 12 questions using a 48-point scale. Individuals with ALS can track their
disease at home using the ALSFRS-R scale, there are several websites that offer that service free of
charge, such as PatientsLikeMe.
-
ALS Research Collaborative (ARC): Through the ALS Research Collaborative (ARC),
researchers at ALS TDI partner with people with ALS around the world to share and gather data
on medical histories, family histories, genetics, biomarkers, and patient cell biology to better
understand the disease. Participants are provided with a secure online portal where their data
is located and easily accessible. They can track their own disease progression and follow how
various interventions impact their symptoms and progression.
-
Clinic Visits: Following clinic visits, individuals with ALS should consider asking for access
to the “data” obtained during the visit, such as the doctor's recorded ALSFRS-R and SVC or
FVC scores. This information is used as enrollment criteria for most clinical trials. Having it on hand
can allow people to quickly determine if they qualify for participation in a trial.
As the disease spreads, many
muscles weaken and start to stiffen. Range of motion exercises will likely be
recommended by physical therapists to help keep muscles loose and prevent the formation of
contractures and muscle pain.
A person with ALS's
breathing may become affected. A BiPAP machine or a
phrenic pacer might be
suggested, particularly to help improve sleeping. A feeding tube might be recommended to help meet
nutritional needs. Medications might be also recommended to help control
pseudobulbar affect
(uncontrolled laughing or crying) or to help reduce muscle spasms.
People with bulbar-onset ALS often work with a speech therapist to keep their ability to speak
for longer. Those with limb-onset ALS may rely on a cane, walker, or wheelchair due to
difficulties walking and maintaining balance.
ALS and Frontotemporal Dementia
In most cases of ALS, cognitive function is not affected. However, over the past 10 years, there
has been an increasing interest in investigating the overlap of ALS with Frontotemporal Dementia (FTD),
another neurological disease characterized by a decline in cognitive function. It is believed that up
to a third of those diagnosed with ALS may be affected by cognitive issues.
As ALS progresses and a person's muscles become paralyzed, they may lose the ability to move
and speak. Many people with ALS may require a wheelchair to get around. Some may communicate through
assistive devices like an eye-tracking device or a letter board. Some people with ALS choose to
undergo a tracheostomy, a procedure in which a tube is surgically inserted into the throat, to
help them breathe. People with late-stage ALS are often cared for at home or in hospice.
There are currently
no effective cures for ALS or treatments to stop disease progression, but
scientists are working hard to develop therapies for this disease. There are currently
only four
treatments approved by the FDA in the United States. They are
riluzole
(marketed as Rilutek or Tiglutik),
edaravone
(marketed as Radicava), a combination of sodium phenylbutyrate and taurursodiol (marketed as Relyvrio), and
tofersen (marketed as Qalsody).
-
Riluzole was approved for treating ALS in the 1990s. Its effects are modest, extending life
by about two to three months.
-
In May 2017, edaravone was approved
by the FDA. Clinical trials of edaravone showed that those who began getting infusions of the
medication early on in their disease had the greatest potential to maintain muscle function.
-
Relyvrio, a combination of two drugs – sodium phenylbutyrate and taurursodiol – was
approved
by the FDA in 2022. The drug, also known as Albrioza in Canada, was shown to slow the loss of
physical function in people with ALS in a phase 2 trial in the US.
While Relyvrio is still currently approved for ALS in the US as of April, 2024, the drug's sponsor, Amylyx, has announced they will voluntarily remove it from market after its Phase 3 trial did not meet primary or secondary endpoints.
-
Tofersen, sold under the brand name Qalsody, is an antisense oligonucleotide (ASO), a short
strand of nucleic acids that can enter a cell and bind with mRNA strands, in this case
effectively “turning down” a gene and disrupting the production of a specific
protein. Although the phase III trial
with 108 participants did not meet its primary functional endpoint, this drug was
approved for use by people with SOD1 ALS in early 2023
based on reductions in levels of neurofilament light chain (NfL), a blood-based biomarker that is
related to neurodegeneration, in participants on active drug.
While none of these treatments have been shown to halt the progression of ALS, some people who take
one or a combination of two or three may experience a positive impact on their progression.
Riluzole, edaravone, Relyvrio, and Qalsody are available today. People with ALS are
encouraged to speak with their doctor to determine if these treatments are right for them.
ALS is a complex, multi-system disease. A growing number of ALS clinics are deploying multidisciplinary
teams to care for and meet the physical, emotional, and nutritional needs of people with ALS. These
palliative care teams include physical, respiratory, speech, and occupational therapists to help people
with ALS breathe easier, keep moving, and stay connected.
Today, there are dozens of potential treatments in clinical trials that are enrolling people with
ALS. You can visit our
ALS Treatments and Drugs
page to read more about potential therapies for ALS. For more information on enrollment and inclusion
criteria for clinical trials, visit our
clinical trials page.
Newly Diagnosed?
Visit our Newly Diagnosed page for tools and resources to help you.
