What Is It?
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed (Gale 2007). ALS was first described in 1869 by French neurologist Jean-Martin Charcot, but it wasn't until 1939 that Lou Gehrig brought national and international attention to the disease when he abruptly retired from baseball after being diagnosed with ALS. Most commonly, the disease strikes people between the ages of 40 and 70, and as many as 30,000 Americans have the disease at any given time.
Description:
Under normal circumstances, muscles move because of messages sent from the brain through the spinal cord to the muscles in the form of electrical impulses. These messages are carried by motor neurons. In ALS, those motor neurons die off and messages from the brain to the muscles do not flow normally. Muscles do not respond when they are supposed to or as well as they should. The death of motor neurons affects voluntary muscles. These muscles are controlled by conscious thought. They include muscles in the legs, arms, and trunk. These muscles normally move when a person wants them to move. "As ALS develops, a person loses that control over these muscles. ALS normally does not affect other kinds of muscles, such as those in the heart or digestive system. It also has no effect on the brain. Thus, ALS patients can usually think normally, although they lose the ability to move (2007)." ALS usually progresses slowly. In about half of all patients, it causes death within three years. About 80 percent of all patients die in less than five years, and a small number (about 10 percent) survive more than eight years.
Symptoms:
The earliest sign of ALS is usually weakness in the arms or legs. This weakness tends to be more apparent on one side of the body than the other. Leg weakness may first become apparent by an increased amount of stumbling on uneven pavement or difficulty in climbing stairs. Arm weakness may lead to difficulty in grasping or holding a cup, for instance, or loss of coordination in fingers. Less commonly, the earliest sign of ALS is weakness in muscles of the mouth. This condition makes it difficult for the patient to chew, swallow and speak. He or she may become hoarse or tired after speaking or may have slurred speech. "Over time, ALS spreads to all voluntary muscle groups in the body. Later symptoms include loss of the ability to walk, to use the arms and hands, to speak clearly or at all, to swallow, and to hold up one's head." Weakness in the muscles of the respiratory (breathing) system can make breathing, coughing, and swallowing difficult. These conditions can result in the inhaling of foods or saliva (aspiration) which, in turn, can cause lung infections (2007). Such infections are a common cause of death in ALS patients. Respiratory problems can be reduced by inserting a mechanical ventilator in the person's throat. This breathing device can extend the patient's life, although muscle weakness and wasting are not reduced. Toward the end of the disease, ALS patients may be able to communicate only by means of eye blinks or a computer-assisted device.
Description:
Under normal circumstances, muscles move because of messages sent from the brain through the spinal cord to the muscles in the form of electrical impulses. These messages are carried by motor neurons. In ALS, those motor neurons die off and messages from the brain to the muscles do not flow normally. Muscles do not respond when they are supposed to or as well as they should. The death of motor neurons affects voluntary muscles. These muscles are controlled by conscious thought. They include muscles in the legs, arms, and trunk. These muscles normally move when a person wants them to move. "As ALS develops, a person loses that control over these muscles. ALS normally does not affect other kinds of muscles, such as those in the heart or digestive system. It also has no effect on the brain. Thus, ALS patients can usually think normally, although they lose the ability to move (2007)." ALS usually progresses slowly. In about half of all patients, it causes death within three years. About 80 percent of all patients die in less than five years, and a small number (about 10 percent) survive more than eight years.
Symptoms:
The earliest sign of ALS is usually weakness in the arms or legs. This weakness tends to be more apparent on one side of the body than the other. Leg weakness may first become apparent by an increased amount of stumbling on uneven pavement or difficulty in climbing stairs. Arm weakness may lead to difficulty in grasping or holding a cup, for instance, or loss of coordination in fingers. Less commonly, the earliest sign of ALS is weakness in muscles of the mouth. This condition makes it difficult for the patient to chew, swallow and speak. He or she may become hoarse or tired after speaking or may have slurred speech. "Over time, ALS spreads to all voluntary muscle groups in the body. Later symptoms include loss of the ability to walk, to use the arms and hands, to speak clearly or at all, to swallow, and to hold up one's head." Weakness in the muscles of the respiratory (breathing) system can make breathing, coughing, and swallowing difficult. These conditions can result in the inhaling of foods or saliva (aspiration) which, in turn, can cause lung infections (2007). Such infections are a common cause of death in ALS patients. Respiratory problems can be reduced by inserting a mechanical ventilator in the person's throat. This breathing device can extend the patient's life, although muscle weakness and wasting are not reduced. Toward the end of the disease, ALS patients may be able to communicate only by means of eye blinks or a computer-assisted device.
What Causes It?
No one knows what causes ALS. One or more factors cause motor neurons in the brain and spinal cord to begin dying off. Disturbed nerve messages can cause abnormal muscle movements that result in twitching and spasms. As muscle cells are not used, they begin to die off. The amount of muscle tissue decreases, causing a condition known as wasting. Researchers have been unsuccessful in finding the cause of motor neuron death. "There is some evidence that free radicals may be involved. Free radicals are very active chemicals that can damage living cells. Defective enzymes may also be a factor in the death of motor neurons. An enzyme is a naturally occurring chemical needed for many chemical reactions that occur in the body (2007)." Additional research is now being conducted to find out more about the cause or causes of ALS. Two major forms of ALS are known: familial and sporadic. About 10 percent of all ALS cases are familial. As the name suggests, familial ALS is thought to be caused by genetic factors. Scientists have found that 15 percent of the people with familial ALS have a mutation in a gene known as SOD-1. A parent with this mutated gene can pass it on to his or her children. Sporadic ALS has no known cause.
According to another pair of researchers, Lokesh C. Wijesekera and P. Nigel Leigh, most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases (2009). In addition, in humans, three mutations in the VEGF gene were found to be associated with increased risk of developing sporadic ALS. The SOD1 gene is located on the long arm of chromosome 21 at position 22.11. The gene normally provides instructions for making an enzyme called superoxide dismutase, which is abundant in cells throughout the body. This enzyme attaches to molecules of copper and zinc to break down toxic, charged oxygen molecules called superoxide radicals. However, there are at least 170 mutations in the SOD1 gene have been found to cause amyotrophic lateral sclerosis. "Most of these mutations change one of the amino acids in the superoxide dismutase enzyme. About half of all Americans with ALS caused by SOD1 gene mutations have a particular mutation that replaces the amino acid alanine with the amino acid valine at position 4 in the enzyme (2009)." The superoxide dismutase enzyme probably gains new, but harmful, properties when altered by SOD1 gene mutations. It is unclear why the nerve cells that control muscle movement, which are affected in ALS, are particularly sensitive to SOD1 gene mutations. Researchers have suggested several ways in which the altered enzyme may cause the death of nerve cells. These possibilities include an accumulation of harmful superoxide radicals, increased production of other types of toxic radicals, increased cell death, or formation of clumps of misfolded superoxide dismutase that may be toxic to cells.
According to another pair of researchers, Lokesh C. Wijesekera and P. Nigel Leigh, most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases (2009). In addition, in humans, three mutations in the VEGF gene were found to be associated with increased risk of developing sporadic ALS. The SOD1 gene is located on the long arm of chromosome 21 at position 22.11. The gene normally provides instructions for making an enzyme called superoxide dismutase, which is abundant in cells throughout the body. This enzyme attaches to molecules of copper and zinc to break down toxic, charged oxygen molecules called superoxide radicals. However, there are at least 170 mutations in the SOD1 gene have been found to cause amyotrophic lateral sclerosis. "Most of these mutations change one of the amino acids in the superoxide dismutase enzyme. About half of all Americans with ALS caused by SOD1 gene mutations have a particular mutation that replaces the amino acid alanine with the amino acid valine at position 4 in the enzyme (2009)." The superoxide dismutase enzyme probably gains new, but harmful, properties when altered by SOD1 gene mutations. It is unclear why the nerve cells that control muscle movement, which are affected in ALS, are particularly sensitive to SOD1 gene mutations. Researchers have suggested several ways in which the altered enzyme may cause the death of nerve cells. These possibilities include an accumulation of harmful superoxide radicals, increased production of other types of toxic radicals, increased cell death, or formation of clumps of misfolded superoxide dismutase that may be toxic to cells.
Renowned scientist Stephen Hawking suffers from amyotrophic lateral sclerosis.
How Do We Fix It?
Treatments:
There is no cure for ALS. There are also no treatments that can significantly alter the course of the disease. In 1998 a new drug, riluzole was approved for use with ALS patients. The drug somewhat reduces the loss of muscle strength. It can extend the life of an ALS patient for an average of three months. No other drug or vitamin has been found to have any effect on the progress of ALS. Physical therapy can often help a patient maintain strength, retain range of motion, and promote general health. Stretching exercises and swimming are often a part of these routines. "Drugs can sometimes be helpful in treating certain symptoms of ALS, such as cramping. Speech therapists can train an ALS patient to deal with problems of swallowing and speaking. A nutritionist can help patients design diets that will be easier to swallow and yet still be nutritious (2007)." In later stages of the disease, mechanical ventilators may be necessary. Mechanical ventilators help patients to breathe more easily and can help prevent aspiration. They can be inserted through the mouth or nose or though an opening in the throat. Modern mechanical ventilators are small and portable. They allow ALS patients some degree of freedom and mobility. Under the best of circumstances, ventilators are somewhat awkward and unpleasant devices. Some ALS patients choose to use them for only short periods of time or not at all.
Theoretical Cure:
"The use of gene therapy approach to deliver neurotrophic factors directly to neurons by means of genetically engineered adeno-associated viruses (AAV) expressing neurotrophic factor genes has been evaluated in SOD1 mouse models with some promising results, but human studies are not yet underway. Another approach is the use of autologous stem cell transplantation," when the stem cells come from your own blood or bone marrow, "but to date there have been no convincing results from human studies (2009)." The recent discovery of the ability to re-programme human skin fibroblast generate pluripotent stem cells (Induced pluripotent stem cells; iPS) would allow patient and disease specific stem cells to produced, leading to better disease models and eventually better autologous cell replacement therapies. Using these stem cells would allow us to significantly slow down the muscle tissue wasting or maybe even stop it completely. According to some tests done on mice, "it slowed the onset of the disease, its progression and prolonged survival fairly significantly. But it did it by protecting the neurons of this animal and also kind of counteracting many of the other disease processes that we started learning were going on in this disease (Gale 2012)."
There is no cure for ALS. There are also no treatments that can significantly alter the course of the disease. In 1998 a new drug, riluzole was approved for use with ALS patients. The drug somewhat reduces the loss of muscle strength. It can extend the life of an ALS patient for an average of three months. No other drug or vitamin has been found to have any effect on the progress of ALS. Physical therapy can often help a patient maintain strength, retain range of motion, and promote general health. Stretching exercises and swimming are often a part of these routines. "Drugs can sometimes be helpful in treating certain symptoms of ALS, such as cramping. Speech therapists can train an ALS patient to deal with problems of swallowing and speaking. A nutritionist can help patients design diets that will be easier to swallow and yet still be nutritious (2007)." In later stages of the disease, mechanical ventilators may be necessary. Mechanical ventilators help patients to breathe more easily and can help prevent aspiration. They can be inserted through the mouth or nose or though an opening in the throat. Modern mechanical ventilators are small and portable. They allow ALS patients some degree of freedom and mobility. Under the best of circumstances, ventilators are somewhat awkward and unpleasant devices. Some ALS patients choose to use them for only short periods of time or not at all.
Theoretical Cure:
"The use of gene therapy approach to deliver neurotrophic factors directly to neurons by means of genetically engineered adeno-associated viruses (AAV) expressing neurotrophic factor genes has been evaluated in SOD1 mouse models with some promising results, but human studies are not yet underway. Another approach is the use of autologous stem cell transplantation," when the stem cells come from your own blood or bone marrow, "but to date there have been no convincing results from human studies (2009)." The recent discovery of the ability to re-programme human skin fibroblast generate pluripotent stem cells (Induced pluripotent stem cells; iPS) would allow patient and disease specific stem cells to produced, leading to better disease models and eventually better autologous cell replacement therapies. Using these stem cells would allow us to significantly slow down the muscle tissue wasting or maybe even stop it completely. According to some tests done on mice, "it slowed the onset of the disease, its progression and prolonged survival fairly significantly. But it did it by protecting the neurons of this animal and also kind of counteracting many of the other disease processes that we started learning were going on in this disease (Gale 2012)."