About FA
What is Friedreich's ataxia?
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 the most common form of hereditary ataxia, affecting about 1 in every 50,000 people (about 6,000) in the United States. Both male and female children can inherit the disorder.
Symptoms typically begin between the ages of 5 and 15 years, although they sometimes appear in adulthood. The first symptom to appear is usually 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) often eventually 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.
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.
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.
It has been proposed that most, if not all, all of the symptoms of Friedreich's Ataxia, characterized by progressive degeneration of the central and peripheral nervous systems, cardiomyopathy, and increased incidence of diabetes mellitus, are related to abnormally low levels of the mitochondrial protein frataxin which gives rise to iron-induced oxidative stress to which nerve and muscle cells are especially vulnerable. The important role attributed to oxidative stress causing damage to mitochondrial DNA, membrane lipids and other cellular constituents provide strong rationale for the use of antioxidants as potential therapies for FRDA. Antioxidant approaches can include drugs that neutralize reactive oxygen species “ROS”, (e.g. hydroxyl radical scavengers), or which inhibit ROS production, (e.g. metal chelators) or which activate mitochondrial activity, (e.g. by a variety of different mechanisms). Importantly, such drugs should be active both in hydrophobic environments to prevent damage to membranes and in aqueous environments to limit damage in the cytosol. In addition, to be effective to treat the disease, antioxidants must have good bioavailability including rapid adsorption and distribution in the body to reach all affected tissue including the brain. Finally any drug used for FRDA, which requires life-long treatment, should have a good safety profile. In this regard, most known antioxidants have the ability to break down during metabolism to form pro-oxidant intermediates that reverse any potential benefit, even causing additional damage to cells. Lack of pro-oxidant activity should therefore be an important consideration in selecting an antioxidant therapy for FRDA.
Intellect Neurosciences developed OX1, a multimodal, metal-binding, amphiphatic antioxidant with a complete lack of pro-oxidant activity which also has good bioavailability and appears to be safe and well tolerated based on preliminary human safety data. Moreover, OX1 has been demonstrated in numerous cell-based and animal models to be extremely effective at protecting cells, especially nerve cells, from highly oxidizing conditions. Also, in contrast to the vast majority of antioxidants OX1 has a rare advantage in that it cannot be metabolized through a pro-oxidant pathway. For these reasons, Intellect scientists identified the potential of OX1 for treatment of FRDA since the drug meets the criteria required of an optimal drug candidate for this indication. The unique combined properties and pharmacological profile of OX1 set it apart from other antioxidant approaches such as those that have been tested and are currently being tested in FRDA with mixed results.
In September, 2011, Intellect Neurosciences, Inc. announced that it had granted an exclusive license to ViroPharma, Inc. regarding certain of Intellect's licensed patents and patent applications related to OX1. ViroPharma plans to develop and commercialize OX1 as a treatment of Friedreich's Ataxia and possibly other diseases for which OX1 may qualify for orphan drug designation.
Under the terms of the Exclusive License Agreement, Intellect has agreed to transfer to ViroPharma all of Intellect's intellectual property rights, data and know-how related to its OX1 research and development program. In return, ViroPharma has paid a $6.5 million up-front licensing fee and will pay additional milestones based upon defined events. The maximum of these milestone payments assuming successful advancement to market could amount to $120 million. In addition, ViroPharma will pay a tiered royalty of up to a maximum of low double digits based on annual net sales.
Source: National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/friedreichs_ataxia/detail_friedreichs_ataxia.htm)
