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Friedreich's ataxia (FRDA or FA) is an autosomal-recessive genetic disease that causes difficulty walking, a loss of sensation in the arms and legs, and impaired speech that worsens over time. Symptoms generally start between 5 and 20 years of age. Many develop
hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...
and require a mobility aid such as a cane, walker, or wheelchair in their teens. As the disease progresses, some affected people lose their sight and hearing. Other complications may include
scoliosis Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
and
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
. The condition is caused by mutations in the ''FXN'' gene on
chromosome 9 Chromosome 9 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome, as they normally do with all chromosomes. Chromosome 9 spans about 138 million base pairs of nucleic acids (the building blocks of ...
, which makes a protein called frataxin. In FRDA, cells produce less frataxin.
Degeneration Degeneracy, degenerate, or degeneration may refer to: Arts and entertainment * ''Degenerate'' (album), a 2010 album by the British band Trigger the Bloodshed * Degenerate art, a term adopted in the 1920s by the Nazi Party in Germany to descri ...
of nerve tissue in the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spin ...
causes the
ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of t ...
; particularly affected are the
sensory neurons Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The ...
essential for directing muscle movement of the arms and legs through connections with the
cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cere ...
. The spinal cord becomes thinner, and nerve cells lose some
myelin sheath Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
. No effective treatment is known, but several therapies are in trials. FRDA shortens life expectancy due to heart disease, but some people can live into their 60s or older. FRDA affects one in 50,000 people in the United States and is the most common inherited ataxia. Rates are highest in people of Western European descent. The condition is named after German physician
Nikolaus Friedreich Nikolaus Friedreich (1 July 1825 in Würzburg – 6 July 1882 in Heidelberg) was a German pathologist and neurologist, and a third generation physician in the Friedreich family. His father was psychiatrist Johann Baptist Friedreich (1796–1862) ...
, who first described it in the 1860s.


Symptoms

Symptoms typically start between the ages of 5 and 15, but in late-onset FRDA, they may occur after age 25 years. The symptoms are broad, but consistently involve gait and limb ataxia, dysarthria and loss of lower limb reflexes.


Classical symptoms

There is some variability in symptom frequency, onset and progression. All individuals with FRDA develop neurological symptoms, including
dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectivel ...
and loss of lower limb reflexes, and more than 90% present with ataxia. Cardiac issues are very common with early onset FRDA . Most individuals develop heart problems such as enlargement of the heart, symmetrical
hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J ...
, heart murmurs, atrial fibrillation,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
,
hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...
, and conduction defects. Scoliosis is present in about 60%. 7% of people with FRDA also have diabetes and having diabetes has an adverse impact on people with FA, especially those that show symptoms when young.


Other symptoms

People who have been living with FRDA for a long time may develop other complications. 36.8% experience decreased visual acuity, which may be progressive and could lead to functional blindness. Hearing loss is present in about 10.9% of cases. Some patients report bladder and bowel symptoms. Advanced stages of disease are associated with supraventricular tachyarrhythmias, most commonly atrial fibrillation. Other later stage symptoms can include, cerebellar effects such as nystagmus, fast
saccadic A saccade ( , French for ''jerk'') is a quick, simultaneous movement of both eyes between two or more phases of fixation in the same direction.Cassin, B. and Solomon, S. ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishi ...
eye movements, dysmetria and loss of coordination ( truncal ataxia, and stomping gait). Symptoms can involve the dorsal column such as the loss of vibratory sensation and proprioceptive sensation. The progressive loss of coordination and muscle strength leads to the full-time use of a wheelchair. Most young people diagnosed with FRDA require mobility aids such as a cane, walker, or wheelchair by early 20s. The disease is progressive, with increasing staggering or stumbling gait and frequent falling. By the third decade, affected people lose the ability to stand or walk without assistance and require a wheelchair for mobility.


Early-onset cases

Non-neurological symptoms such as
scoliosis Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
, pes cavus, cardiomyopathy and diabetes are more frequent amongst the early-onset cases.


Genetics

FRDA is an autosomal-recessive disorder that affects a gene (''FXN'') on chromosome 9, which produces an important protein called frataxin. In 96% of cases, the mutant ''FXN'' gene has 90–1,300 GAA trinucleotide repeat expansions in
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene ...
1 of both
alleles An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...
. This expansion causes
epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are " ...
changes and formation of
heterochromatin Heterochromatin is a tightly packed form of DNA or '' condensed DNA'', which comes in multiple varieties. These varieties lie on a continue between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a rol ...
near the repeat. The length of the shorter GAA repeat is correlated with the age of onset and disease severity. The formation of heterochromatin results in reduced transcription of the gene and low levels of frataxin. People with FDRA might have 5-35% of the frataxin protein compared to healthy individuals.
Heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
carriers of the mutant FXN gene have 50% lower frataxin levels, but this decrease is not enough to cause symptoms. In about 4% of cases, the disease is caused by a (
missense In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense ...
,
nonsense Nonsense is a communication, via speech, writing, or any other symbolic system, that lacks any coherent meaning. Sometimes in ordinary usage, nonsense is synonymous with absurdity or the ridiculous. Many poets, novelists and songwriters have us ...
, or intronic)
point mutation A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences ...
, with an expansion in one
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...
and a
point mutation A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences ...
in the other. A missense point mutation can have milder symptoms. Depending on the point mutation, cells can produce no frataxin, nonfunctional frataxin, or frataxin that is not properly localized to the mitochondria.


Pathophysiology

FRDA affects the nervous system, heart, pancreas, and other systems. Degeneration of nerve tissue in the spinal cord causes ataxia. The sensory neurons essential for directing muscle movement of the arms and legs through connections with the cerebellum are particularly affected. The disease primarily affects the spinal cord and peripheral nerves. The spinal cord becomes thinner and nerve cells lose some
myelin sheath Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
. The diameter of the spinal cord is smaller than that of unaffected individuals mainly due to smaller dorsal root ganglia. The
motor neuron A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly ...
s of the spinal cord are affected to a lesser extent than sensory neurons. In peripheral nerves, a loss of large myelinated sensory fibers occurs. Structures in the brain are also affected by FRDA, notably the dentate nucleus of the cerebellum. The heart often develops some fibrosis, and over time, develops left-ventricle hypertrophy and dilatation of the left ventricle.


Frataxin

The exact role of frataxin remains unclear. Frataxin assists
iron-sulfur protein Iron–sulfur proteins (or iron–sulphur proteins in British spelling) are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur c ...
synthesis in the electron transport chain to generate
adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms ...
, the energy molecule necessary to carry out metabolic functions in cells. It also regulates iron transfer in the mitochondria by providing a proper amount of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen ...
(ROS) to maintain normal processes. One result of frataxin deficiency is mitochondrial iron overload, which damages many proteins due to effects on cellular metabolism. Without frataxin, the energy in the mitochondria falls, and excess iron creates extra ROS, leading to further cell damage. Low frataxin levels lead to insufficient biosynthesis of iron–sulfur clusters that are required for mitochondrial electron transport and assembly of functional
aconitase Aconitase (aconitate hydratase; ) is an enzyme that catalyses the stereo-specific isomerization of citrate to isocitrate via ''cis''-aconitate in the tricarboxylic acid cycle, a non-redox-active process. Image:Citrate wpmp.png, Image:Cis ...
and iron dysmetabolism of the entire cell.


Diagnosis

Balance difficulty, loss of proprioception, an absence of reflexes, and signs of other neurological problems are common signs from a physical examination. Diagnostic tests are made to confirm a physical examination such as electromyogram, nerve conduction studies, electrocardiogram, echocardiogram,
blood test A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a ch ...
s for elevated glucose levels and vitamin E levels, and scans such as X-ray radiograph for scoliosis. MRI and
CT scans A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
of brain and spinal cord are done to rule out other neurological conditions. Finally, a
genetic test Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
is conducted to confirm. Other diagnoses might include Charcot-Marie-Tooth types 1 and 2, ataxia with
vitamin E deficiency Vitamin E deficiency in humans is a very rare condition, occurring as a consequence of abnormalities in dietary fat absorption or metabolism rather than from a diet low in vitamin E. Collectively the EARs, RDAs, AIs and ULs for vitamin E and other ...
, ataxia-oculomotor apraxia types 1 and 2, and other early-onset ataxias.


Management

Physical therapists play a critical role in educating on correct posture, muscle use, and the identification and avoidance of features that aggravate spasticities such as tight clothing, poorly adjusted wheelchairs, pain, and infection.


Rehabilitation

Physical therapy typically includes intensive motor coordination, balance, and stabilization training to preserve gains. Low intensity strengthening exercises are incorporated to maintain functional use of the upper and lower extremities. Stretching and muscle relaxation exercises can be prescribed to help manage spasticity and prevent deformities. Other physical therapy goals include increased transfer and locomotion independence, muscle strengthening, increased physical resilience, "safe fall" strategy, learning to use mobility aids, learning how to reduce the body's energy expenditure, and developing specific breathing patterns. Speech therapy can improve voice quality.


Devices

Well-fitted orthoses can promote correct posture, support normal joint alignment, stabilize joints during walking, improve range of motion and gait, reduce
spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles ...
, and prevent foot deformities and scoliosis. Functional electrical stimulation or transcutaneous nerve stimulation devices may alleviate symptoms. As progression of ataxia continues, assistive devices such as a cane, walker, or wheelchair may be required for mobility and independence. A standing frame can help reduce the secondary complications of prolonged use of a wheelchair.


Medication and surgery

Cardiac abnormalities can be controlled with
ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volum ...
s such as
enalapril Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosem ...
,
ramipril Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 yea ...
,
lisinopril Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to ...
, or
trandolapril Trandolapril is an ACE inhibitor used to treat high blood pressure. It may also be used to treat other conditions. It is similar in structure to another ACE Inhibitor, Ramipril but has a cyclohexane group. It also is a pro-drug and must get metab ...
, sometimes used in conjunction with
beta blockers Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are a ...
. Affected people who also have symptomatic
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
may be prescribed eplerenone or
digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...
to keep cardiac abnormalities under control. Surgery may correct deformities caused by abnormal muscle tone. Titanium screws and rods inserted in the spine help prevent or slow the progression of scoliosis. Surgery to lengthen the
Achilles tendon The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcane ...
can improve independence and mobility to alleviate
equinus deformity Toe walking refers to a condition where a person walks on their toes without putting much or any weight on the heel or any other part of the foot. This term also includes the inability to connect one's foot fully to the ground while in the standi ...
. An automated
implantable cardioverter-defibrillator An implantable cardioverter-defibrillator (ICD) or automated implantable cardioverter defibrillator (AICD) is a device implantable inside the body, able to perform defibrillation, and depending on the type, cardioversion and pacing of the ...
can be implanted after a severe heart failure.


Prognosis

The disease evolves differently in different people. In general, those diagnosed at a younger age or with longer GAA triplet expansions tend to have more severe symptoms. Congestive heart failure and abnormal heart rhythms are the leading causes of death, but people with fewer symptoms can live into their 60s or older.


Epidemiology

FRDA affects Indo-European populations. It is rare in East Asians, sub-Saharan Africans, and Native Americans. FRDA is the most prevalent inherited ataxia, affecting approximately 1 in 40,000 with European descent. Males and females are affected equally. The estimated carrier prevalence is 1:100. A 1990–1996 study of Europeans calculated the incidence rate was 2.8:100,000. The prevalence rate of FRDA in Japan is 1:1,000,000. FRDA follows the same pattern as
haplogroup R1b Haplogroup R1b (R-M343), previously known as Hg1 and Eu18, is a human Y-chromosome haplogroup. It is the most frequently occurring paternal lineage in Western Europe, as well as some parts of Russia (e.g. the Bashkirs) and pockets of Central A ...
. Haplogroup R1b is the most frequently occurring paternal lineage in Western Europe. FRDA and Haplogroup R1b are more common in northern Spain, Ireland, and France, rare in Russia and Scandinavia, and follow a gradient through central and eastern Europe. A population carrying the disease went through a
population bottleneck A population bottleneck or genetic bottleneck is a sharp reduction in the size of a population Population typically refers to the number of people in a single area, whether it be a city or town, region, country, continent, or the world. Go ...
in the Franco-Cantabrian region during the last ice age.


History

The condition is named after the 1860s German
pathologist Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in t ...
and
neurologist Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
,
Nikolaus Friedreich Nikolaus Friedreich (1 July 1825 in Würzburg – 6 July 1882 in Heidelberg) was a German pathologist and neurologist, and a third generation physician in the Friedreich family. His father was psychiatrist Johann Baptist Friedreich (1796–1862) ...
. Friedreich reported the disease in 1863 at the
University of Heidelberg } Heidelberg University, officially the Ruprecht Karl University of Heidelberg, (german: Ruprecht-Karls-Universität Heidelberg; la, Universitas Ruperto Carola Heidelbergensis) is a public university, public research university in Heidelberg, B ...
. Further observations appeared in a paper in 1876.
Frantz Fanon Frantz Omar Fanon (, ; ; 20 July 1925 – 6 December 1961), also known as Ibrahim Frantz Fanon, was a French West Indian psychiatrist, and political philosopher from the French colony of Martinique (today a French department). His works have ...
wrote his medical thesis on FRDA, in 1951. A 1984 Canadian study traced 40 cases to one common ancestral couple arriving in
New France New France (french: Nouvelle-France) was the area colonized by Kingdom of France, France in North America, beginning with the exploration of the Gulf of Saint Lawrence by Jacques Cartier in 1534 and ending with the cession of New France to King ...
in 1634. FRDA was first linked to a GAA repeat expansion on chromosome 9 in 1996.


Research

Active research is ongoing to find a treatment. Patients can enroll in a registry to make clinical trial recruiting easier. The Friedreich's Ataxia Global Patient Registry is the only worldwide registry of Friedreich's ataxia patients to characterize the symptoms and establish the rate of disease progression. The Friedreich's Ataxia App is the only global community app which enables novel forms of research. As of May 2021, research continues along the following paths.


Improve mitochondrial function and reduce oxidative stress

* Reata Pharmaceuticals developed
RTA 408 Omaveloxolone, sold under the brand name Skyclarys, is a medication used for the treatment of Friedreich's ataxia. It is taken by mouth. The most common side effects include an increase in alanine transaminase and an increase of aspartate ...
(
Omaveloxolone Omaveloxolone, sold under the brand name Skyclarys, is a medication used for the treatment of Friedreich's ataxia. It is taken by mouth. The most common side effects include an increase in alanine transaminase and an increase of aspartate am ...
or Omav) to target activation of a transcriptional factor, Nrf2. Nrf2 is decreased in FRDA cells.. * PTC-743 (formerly EPI-743) is being developed by PTC Therapeutics. PTC-743 is a para-benzoquinone and targets the NAD(P)H dehydrogenase (quinone 1) (NQO1) enzyme to increase the biosynthesis of
glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
. * Retrotope is advancing
RT001 Di-deuterated ethyl linoleate (also known as RT001, di-deuterated linoleic acid ethyl ester, 11,11-''d2''-ethyl linoleate, or ethyl 11,11-''d2''-linoleate) is an experimental, orally-bioavailable synthetic deuterated polyunsaturated fatty acid (PU ...
. RT001 is a deuterated synthetic homologue of ethyl linoleate, an essential omega-6 polyunsaturated fatty acid which is one of the major components of lipid membranes, particularly in mitochondria. Oxidation damage might be reduced if the
polyunsaturated fatty acid Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic proper ...
s in the lipids were made more rigid and less susceptible to oxidation by the replacement of
hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...
atoms with the heavy hydrogen isotope
deuterium Deuterium (or hydrogen-2, symbol or deuterium, also known as heavy hydrogen) is one of two Stable isotope ratio, stable isotopes of hydrogen (the other being Hydrogen atom, protium, or hydrogen-1). The atomic nucleus, nucleus of a deuterium ato ...
.


Modulation of frataxin controlled metabolic pathways

* Dimethyl fumarate has been shown to increase frataxin levels in FRDA cells, mouse models, and humans. DMF showed an 85% increase in frataxin expression over 3 months in multiple sclerosis .


Frataxin replacements or stabilizers

* EPO mimetics are orally available peptide imitations of
erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bon ...
. They are small molecules erythropoietin receptor agonists designed to activate the tissue-protective erythropoietin receptor. * Etravirine, an antiviral drug used to treat HIV, was found in a drug repositioning screening to increase frataxin levels in peripheral cells. Fratagene Therapeutics is developing a small molecule called RNF126 to inhibit an enzyme which degrades frataxin.


Increase frataxin gene expression

*
Resveratrol Resveratrol (3,5,4′-trihydroxy-''trans''-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources ...
might improve mitochondrial function. *
Nicotinamide Niacinamide or Nicotinamide (NAM) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) ma ...
(vitamin B3) was found effective in preclinical FRDA models and well tolerated. * An
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
-based approach might unsilence the FXN gene and increase the expression of frataxin. Non-coding RNA ( ncRNA) could be responsible for directing the localized
epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are " ...
silencing of the FXN gene. *
Lentivirus ''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Le ...
-mediated delivery of the FXN gene has been shown to increase frataxin expression and prevent DNA damage in human and mouse
fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
. * CRISPR Therapeutics received a grant from the Friedreich's Ataxia Research Alliance to investigate gene editing as a potential treatment for the disease in 2017.


Society and culture

'' The Cake Eaters'' is a 2007 independent drama film that stars
Kristen Stewart Kristen Jaymes Stewart (born April 9, 1990) is an American actress. The world's highest-paid actress in 2012, she has received various accolades, including a British Academy Film Award and a César Award, in addition to nominations for an Ac ...
as a young woman with FRDA. ''
The Ataxian ''The Ataxian'' is a documentary film of Kyle Bryant, a sufferer of Friedreich's ataxia. The film premiered at the Dances With Films Festival in 2015. Synopsis The movie tells how Bryant lost the ability to play his favorite sports and walk. ...
'' is a documentary that tells the story of
Kyle Bryant Kyle Bryant (October 5, 1981) is an athlete, speaker and the spokesperson for the Friedreich's Ataxia Research Alliance (FARA). Bryant is the founder and event director of rideATAXIA – a nationwide bike ride fundraiser benefiting FARA. Early li ...
, an athlete with FRDA who completes a long-distance bike race in an adaptive "trike" to raise money for research. Dynah Haubert spoke at the 2016 Democratic National Convention about supporting Americans with disabilities. Geraint Williams in an athlete affected by FRDA who is known for scaling
Mount Kilimanjaro Mount Kilimanjaro () is a dormant volcano in Tanzania. It has three volcanic cones: Kibo, Mawenzi, and Shira. It is the highest mountain in Africa and the highest free-standing mountain above sea level in the world: above sea level and ab ...
in an adaptive wheelchair. Shobhika Kalra is an activist with FRDA who helped build over 1000 wheelchair ramps across the
United Arab Emirates The United Arab Emirates (UAE; ar, اَلْإِمَارَات الْعَرَبِيَة الْمُتَحِدَة ), or simply the Emirates ( ar, الِْإمَارَات ), is a country in Western Asia ( The Middle East). It is located at ...
in 2018 to try to make
Dubai Dubai (, ; ar, دبي, translit=Dubayy, , ) is the most populous city in the United Arab Emirates (UAE) and the capital of the Emirate of Dubai, the most populated of the 7 emirates of the United Arab Emirates.The Government and Politics ...
fully wheelchair-friendly by 2020.


References


External links


Friedreich's Ataxia Global Patient RegistryNIH's FRDA information page
{{DEFAULTSORT:Friedreich's Ataxia Systemic atrophies primarily affecting the central nervous system Autosomal recessive disorders Mitochondrial diseases Trinucleotide repeat disorders Rare diseases