Friedreich’s Ataxia
Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system, resulting in symptoms ranging from gait disturbance to speech problems; it can also lead to heart disease and diabetes.
The ataxia of Friedreich's ataxia results from the degeneration of nerve tissue in the spinal cord, in particular sensory neurons essential (through connections with the cerebellum) for directing muscle movement of the arms and legs. Friedreich's ataxia (also called FA or FRDA) is a rare inherited disease that causes nervous system damage and movement problems. It usually begins in childhood and leads to impaired muscle coordination (ataxia) that worsens over time. The disorder is named after Nicholaus Friedreich, a German doctor who first described the condition in the 1860s.
In Friedreich’s ataxia the spinal cord and peripheral nerves degenerate, becoming thinner. The cerebellum, part of the brain that coordinates balance and movement, also degenerates to a lesser extent. This damage results in awkward, unsteady movements and impaired sensory functions. The disorder also causes problems in the heart and spine, and some people with the condition develop diabetes. The disorder does not affect thinking and reasoning abilities (cognitive functions).
Friedreich’s ataxia is caused by a defect (mutation) in a gene labeled FXN. The disorder is recessive, meaning it occurs only in someone who inherits two defective copies of the gene, one from each parent. Although rare, Friedreich’s ataxia is the most common form of hereditary ataxia, affecting about one in every 50,000 people in the United States. Both male and female children can inherit the disorder
The spinal cord becomes thinner and nerve cells lose some of their myelin sheath (the insulating covering on some nerve cells that helps conduct nerve impulses).
Studies have revealed that frataxin is an important mitochondrial protein for proper function of several organs. Yet in people with the disease, the amount of frataxin in affected cells is severely reduced. It is believed that the loss of frataxin makes the nervous system, heart, and pancreas particularly susceptible to damage from free radicals (produced when the excess iron reacts with oxygen). Once certain cells in these tissues are destroyed by free radicals, they cannot be replaced. Nerve and muscle cells also have metabolic needs that may make them particularly vulnerable to this damage. Free radicals have been implicated in other degenerative diseases such as Parkinson's and Alzheimer's diseases.
Symptoms
Symptoms are caused by the wearing away of structures in areas of the brain and spinal cord that control coordination, muscle movement, and some sensory functions. Symptoms generally begin in childhood before puberty, and may include:
- Abnormal speech
- Changes in vision, particularly color vision
- Decrease in ability to feel vibrations in lower limbs
- Foot problems, such as hammer toe and high arches
- Hearing loss occurs in about 10% of patients
- Jerky eye movements
- Loss of coordination and balance, which leads to frequent falls
- Muscle weakness
- No reflexes in the legs
- Unsteady gait and uncoordinated movements (ataxia) gets worse with time
Muscle problems lead to changes in the spine, which may result in scoliosis or hyphoscoliosis.
Heart disease usually develops and may lead to heart failure. Death may result from heart failure or dysrhythmias that do not respond to treatment. Diabetes may develop in later stages of the disease
What are the signs and symptoms?
Symptoms typically begin between the ages of 5 and 15 years, although they sometimes appear in adulthood and on rare occasions as late as age 75. The first symptom to appear is usually gait ataxia, or difficulty walking. The ataxia gradually worsens and slowly spreads to the arms and the trunk. There is often loss of sensation in the extremities, which may spread to other parts of the body. Other features include loss of tendon reflexes, especially in the knees and ankles. Most people with Friedreich's ataxia develop scoliosis (a curving of the spine to one side), which often requires surgical intervention for treatment.
Dysarthria (slowness and slurring of speech) develops and can get progressively worse. Many individuals with later stages of Friedreich’s ataxia develop hearing and vision loss.
Other symptoms that may occur include chest pain, shortness of breath, and heart palpitations. These symptoms are the result of various forms of heart disease that often accompany Friedreich's ataxia, such as hypertrophic cardiomyopathy (enlargement of the heart), myocardial fibrosis (formation of fiber-like material in the muscles of the heart), and cardiac failure. Heart rhythm abnormalities such as tachycardia (fast heart rate) and heart block (impaired conduction of cardiac impulses within the heart) are also common.
About 20 percent of people with Friedreich's ataxia develop carbohydrate intolerance and 10 percent develop diabetes. Most individuals with Friedreich’s ataxia tire very easily and find that they require more rest and take a longer time to recover from common illnesses such as colds and flu.
The rate of progression varies from person to person. Generally, within 10 to 20 years after the appearance of the first symptoms, the person is confined to a wheelchair, and in later stages of the disease, individuals may become completely incapacitated.
Friedreich's ataxia can shorten life expectancy, and heart disease is the most common cause of death. However, some people with less severe features of Friedreich's ataxia live into their sixties, seventies, or older.
The triplet repeat expansion greatly disrupts the normal production of frataxin. Frataxin is found in the energy-producing parts of the cell called mitochondria. Research suggests that without a normal level of frataxin, certain cells in the body (especially peripheral nerve, spinal cord, brain and heart muscle cells) cannot effectively produce energy and have been hypothesized to have a buildup of toxic byproducts leading to what is called “oxidative stress.” It also may lead to increased levels of iron in the mitochondria. When the excess iron reacts with oxygen, free radicals can be produced. Although free radicals are essential molecules in the body's metabolism, they can also destroy cells and harm the body.
Based upon this information, scientists and physicians have tried to reduce the levels of free radicals, also called oxidants, using treatment with “antioxidants”. Initial clinical studies in Europe suggested that antioxidants like coenzyme Q10, vitamin E, and idebenone might offer individuals some limited benefit. However, recent clinical trials in the United States and Europe have not revealed effectiveness of idebenone in people with Friedreich’s ataxia, but more powerful modified forms of this agent and other antioxidants are in trials at this time. There is also a clinical trial to examine the efficacy of selectively removing excess iron from the mitochondria.
Scientists also are exploring ways to increase frataxin levels through drug treatments, genetic engineering and protein delivery systems. Several compounds that are directed at increasing levels of frataxin may be brought to clinical trials in the near future.
As with many degenerative diseases of the nervous system, there is currently no cure or effective treatment for Friedreich's ataxia. However, many of the symptoms and accompanying complications can be treated to help individuals maintain optimal functioning as long as possible. Doctors can prescribe treatments for diabetes, if present; some of the heart problems can be treated with medication as well. Orthopedic problems such as foot deformities and scoliosis can be corrected with braces or surgery. Physical therapy may prolong use of the arms and legs. Advances in understanding the genetics of Friedreich's ataxia are leading to breakthroughs in treatment. Research has moved forward to the point where clinical trials of proposed treatments are presently occurring for Friedreich’s ataxia.
Complications
- Diabetes
- Heart failure or heart disease
- Loss of ability to move around
Low intensity strengthening exercises should also be incorporated to maintain functional use of the upper and lower extremities.
Stretching exercises can be prescribed to help relieve tight musculature due to scoliosis and pes cavus deformity (hollow foot)-deformity of foot where instep is very high. Surgery because of difficulty is only done if there is severe pain.
A person suffering from Friedreich's Ataxia may require some surgical interventions (mainly for the spine and heart).
Friedreich's ataxia slowly gets worse and causes problems performing everyday activities. Most patients need to use a wheelchair within 15 years of the disease's start. The disease may lead to early death.
Currently, there is a medication approved in Canada called idebenone. This prescription medicine is also under regulatory review in Europe and Switzerland. In both the United States and in Europe there are two Phase III clinical trials on going with idebenone. As of 2009, Persons with Friedreich’s ataxia may also benefit from a conservative treatment approach for the management of symptoms
How Can Medical Marijuana Help?
- Cannabinoids act as antioxidants to reduce free radical levels.
- Cannabinoids are pain relievers. Suppress transmission of pain signals in the brain. Marijuana has a neurochemical effect on pain.
- Cannabinoids relieve “jerky eye movements”
- Cannabinoids relax tight muscles (spine)
- Cannabinoids help relieve depression.
- Cannabinoids help relieve muscle spasms and leg cramps
- Cannabinoids help relieve stress
So far, there is no effective treatment ( except medical marijuana for symptom relief) and there is no cure for Friedreich’s ataxia. Researchers around the world are getting closer to finding the answers.
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