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 diligently to find treatments.
Watch our TEDEd Video: Why is it So Hard to Cure ALS?
Familial ALS:
15% of cases are known as familial ALS, in which a specific ALS-related
genetic mutation is inherited and passed down from generation to generation.
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Over 40 ALS-related genes have now been identified [1].
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The most common known genetic mutation in ALS is in the C9orf72 gene, which accounts
for approximately 30 to 40% of all familial ALS cases [1]. These mutations are also
known to cause Frontotemporal Dementia (FTD), another neurodegenerative disease that
primarily affects behavior and the ability to think and reason.
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Mutations in the SOD1 gene comprise around 20% of familial ALS, and TARDBP and FUS
gene mutations each account for about five percent of familial cases.
Sporadic ALS:
The remaining 85% of cases are known as sporadic ALS, meaning there is no
known history of the disease in a family. However, genetic factors may still play a role.
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There are many theories outlining potential causes of ALS including oxidative stress,
mitochondrial dysfunction, immune system overactivity, glutamate toxicity, and exposure to toxic substances.
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Studies have shown that people who have served in the military are more likely to develop
ALS than the general population [2], [3].
It is important to note that familial ALS and sporadic ALS appear to be clinically indistinguishable from one another.
Who Gets ALS?
ALS can affect anyone. 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, 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]. Further
research is needed to understand the reasons for these differences.
A series of clinical procedures may also be conducted to rule out other conditions
whose symptoms closely resemble ALS, including infections like Lyme disease and other
neurological disorders such as multifocal motor neuropathy. 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 ALS TDI's
ALS Trial Navigator.
What Procedures are Used to Diagnose ALS?
Some of the procedures a person may undergo on their way to an ALS diagnosis include:
Genetic testing
When a
familial case of ALS
(fALS) is suspected, genetic testing may be recommended. Commercially available tests can
identify dozens of ALS-related genes. People who undergo genetic testing are typically
provided genetic counseling to help them interpret their results.
Electromyography and nerve conduction studies
These tests enable clinicians to determine whether motor nerves are connected to
the muscles and are working properly. Nerve conduction studies (NCS) test whether
the motor nerves can send signals of sufficient strength to 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.
Other tests
Other tests: These can include blood, urine tests, and spinal taps. Researchers
hope to expedite the diagnostic process by developing tools that directly indicate
whether a person has the disease.
Magnetic Resonance Imaging (MRI)
MRI enables clinicians to examine organs and tissues including the brain and
spinal cord. An MRI can help rule out several conditions, including brain tumors,
multiple sclerosis,
and certain disorders of the
spinal cord.
Emerging Tools for Diagnosis
An increasing number of researchers suspect that
MRI
technology may do more than rule out other diseases—it could potentially detect whether a person has ALS. Researchers
also hope that certain
biomarkers can
be used to identify people who are at high risk of developing ALS
before they show symptoms.
Additionally, electrical impedance myography (EIM) is being developed to identify changes in affected
muscles. Scientists hope this tool might also predict the spread of ALS through the body and aid in the
development of treatments for the disease.
Early Symptoms of ALS
Most people's early ALS symptoms include
muscle cramps, spasms, or
twitching
(
fasciculations) in one or more 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.
Progressive Symptoms of ALS
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.
Breathing may become affected in a person with ALS. A BiPAP machine might be suggested,
particularly to help improve sleeping. A feeding tube might be recommended to help meet nutritional needs.
Medications might also be 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 maintain their ability to speak for
longer or to implement assistive communication devices. Those with limb-onset ALS may rely on a cane,
walker, or wheelchair due to difficulties walking and maintaining balance.
Advanced Symptoms of ALS
As ALS progresses and a person's muscles become paralyzed, they may lose the ability to
move and speak. Many people with ALS 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 and coupled with a
ventilator to help them breathe. People with advanced ALS are often cared for at home or in hospice.
Monitoring 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 methods for monitoring ALS include:
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Spirometry: These are tests that measure 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).
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ALS Functional Rating Scale-Revised (ALSFRS-R): The ALSFRS-R is a
questionnaire that measures a person's functional capacities, such as breathing, speaking, sleeping,
swallowing, walking, and fine motor skills. 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.
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ALS Research Collaborative (ARC) Study: Through
the ALS Research Collaborative (ARC), Study, ALS TDI researchers partner with people with ALS worldwide
to collect data on medical and family histories, genetics, biomarkers, and patient cell biology, helping
to deepen understanding of the disease.ARC participants can access their data in a secure online portal. There,
they can track their symptoms and monitor the impact of interventions.
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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.
ALS and Frontotemporal Dementia
In most cases of ALS, cognitive function is not affected. However, in some cases
Frontotemporal Dementia (FTD),
another neurological disease characterized by a decline in cognitive function, can overlap with
ALS. It is believed that up to one-third of those diagnosed with ALS may experience some cognitive issues.
There are currently
three FDA-approved treatments for ALS that are marketed in the United States
and may provide some benefits to people living with ALS. They are
riluzole
(marketed as Rilutek or Tiglutik),
edaravone
(marketed as Radicava), and tofersen (marketed as Qalsody). A fourth treatment, a combination of sodium
phenylbutyrate and taurursodiol (marketed as Relyvrio), is currently approved but has been voluntarily pulled
from the market by its sponsor due to a lack of efficacy in a confirmatory phase 3 trial.
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Riluzole was approved for treating ALS in the 1990s. Its effects
are modest, extending life by about two to three months.
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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 longer.
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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 a phase 3 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.
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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 December 2024, the drug's sponsor, Amylyx, has voluntarily removed it from market
after a phase 3 trial did not meet its primary or secondary endpoints.
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, and Qalsody are available today. People with ALS are encouraged to speak with their doctor to
determine if these treatments are right for them.
What is the Role of ALS Clinics?
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 care
teams include physical, respiratory, speech, and occupational therapists to help people with ALS breathe
more easily, keep moving, and stay connected. A
database of ALS clinics in the United States
is available through the
ALS Geospatial Hub.
What Clinical Trials Exist for ALS?
Today, there are multiple potential treatments in clinical trials enrolling people with ALS.
You can visit our ALS Trial Navigator to learn about currently
enrolling clinical trials for ALS. Use our
Guided Trial Finder
tool to find a tailored list of trials based on your needs and criteria.
Want Additional Information?
Are you newly diagnosed with ALS?
Join the ARC Study to begin sharing your data from home and make an impact in ALS research.
www.als.net/arc
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