Every 90 minutes someone is diagnosed with amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative
disorder. Each case is different, and the community of people with ALS and the care providers involved with ALS
TDI share their experiences to help those newly diagnosed and their families. Advancements in ALS research have
provided significant new insights into ALS, how to stratify those diagnosed, and develop effective treatments
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 3-5 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 are two medications that have been approved by the FDA as treatments for ALS;
Riluzole and Radicava. People diagnosed with
ALS are encouraged to speak with their doctors about these approaches. While neither were found
in clinical trials to be broadly disease modifying (stopping disease) in all people with ALS,
many people taking them do experience some impact on their disease progression (which can be
monitored in part through participation in our
Precision Medicine Program).
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.
The ALS Therapy Development Institute is YOUR lab. It is funded by people just like you. Click, learn more.
What is ALS? Why is it so hard to cure ALS? - Fernando G. Vieira
The Precision Medicine Program is now enrolling people with ALS. Sign-up to join hundreds of others
in sharing data to help speed up clinical trials and end ALS.
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 person with ALS's functional abilities
Most people with ALS live about 3-5 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:
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 for ALS, however scientists are working hard to develop therapies for this disease. There are
currently only two treatments approved by the FDA in the United States. They are
riluzole (marketed as Rilutek),
(marketed as Radicava).
Much more is known about the use of Rilutek in ALS as it was approved in the 1990s. Its effects are
modest, extending life by about two to three months. More recently,
Radicava was approved
by the FDA in May 2017 and people with ALS can now
access the drug. Clinical
trials of Radicava showed the greatest potential impact on maintaining function was in those who
started getting infusions of the medication early on in their disease. While, neither of these
treatments have been shown to halt the progression of ALS, some people who take either or both of
them may experience a positive impact on their progression. Both riluzole and edaravone are
available today and patients are encouraged to speak with their doctor about them to determine if
they are right for them.
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 care providers.
Today, there are dozens of clinical trials evaluating potential treatments enrolling people with
ALS and their families. For more information on enrollment and inclusion criteria, visit our
clinical trials page.
Researchers are developing a number of treatment strategies to fight ALS. The most recent advancements in
ALS research were recapped on this webinar which discussed edaravone, tirasemtiv, NP001, NurOwn and many
other topics. Immune system-modulating drugs including Anelixis Therapeutics AT-1501
and Neuraltus Pharmaceuticals' NP001 hope to slow ALS in its tracks by reducing neuroinflammation. Stem
cell-based strategies including Cedar Sinai’s GDNF trial, Neuralstem's NSI-566, Brainstorm's NurOwn hope to
shield motor neurons from destruction. And, potential muscle boosters including Cytokinetics' tirasemtiv
(CK-357) hope to help people breathe easier and keep muscles moving. Edaravone
was approved for use in Japan against ALS in 2015 is before the FDA for approval in 2017 and
masitinib from AB Science is right
behind it. There are many other potential treatments in the works in earlier stage clinical trials that are
also seeking volunteers. For the latest clinical trial information subscribe to our
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.
While there is no cure of effective treatment for ALS yet, the ALS Therapy Development Institute is 100% focused on
changing that reality for people living with ALS today. Through this work, ALS TDI scientists continue to enable
significant advancements, new clinical trials and trial designs, and novel research that transforms people with ALS
and their care providers into partners in research, rather than simply research subjects. Join us today, start now,