Friedreich's Ataxia 1976 — An Overview

SUMMARY:The prospective investigation of 50 cases of possible Friedreich's ataxia has permitted the clinical and biochemical delineation of the typical disease and an hypothesis on its pathogenesis. A tentative definition of the disorder could read: “Friedreich's ataxia is a progressive degenerative disease always inherited in an autosomal recessive fashion and characterized by a cardiomyopathy and a ganglioneuropathy with dying back phenomenon. It is probably secondary to a defect in the membrane transport of taurine and β -alanine and/or a defect in the regulation of pyruvate oxidation.” The existence of two pathogenetically distinct distinct entities with the same phenotype is a strong possibility.

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Future Prospects of Gene Therapy for Friedreich’s Ataxia

International Journal of Molecular Sciences ◽

10.3390/ijms22041815 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1815 ◽

Cited By ~ 1

Author(s):

Gabriel Ocana-Santero ◽

Javier Díaz-Nido ◽

Saúl Herranz-Martín

Keyword(s):

Gene Therapy ◽

Viral Vectors ◽

Autosomal Recessive ◽

State Of The Art ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

First Intron ◽

Progressive Neurodegeneration ◽

Feasible Solutions ◽

Neurogenetic Disease

Friedreich’s ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich’s ataxia. A plausible therapeutic approach is gene therapy. Indeed, Friedreich’s ataxia mouse models have been treated with viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, gene therapy is increasingly consolidating as one of the most promising therapies. However, several hurdles have to be overcome, including immunotoxicity and pheno-toxicity. We review the state of the art of gene therapy in Friedreich’s ataxia, addressing the main challenges and the most feasible solutions for them.

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Mitochondrial dysfunction in the neuro-degenerative and cardio-degenerative disease, Friedreich's ataxia

Neurochemistry International ◽

10.1016/j.neuint.2017.08.002 ◽

2018 ◽

Vol 117 ◽

pp. 35-48 ◽

Cited By ~ 22

Author(s):

Shannon Chiang ◽

Danuta S. Kalinowski ◽

Patric J. Jansson ◽

Des R. Richardson ◽

Michael L.-H. Huang

Keyword(s):

Mitochondrial Dysfunction ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Degenerative Disease

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Autosomal Recessive Hereditary Ataxias Except Friedreich’s Ataxia

Journal of Parkinson’s Disease and Movement Disorders ◽

10.5606/phhb.dergisi.2015.02 ◽

2015 ◽

Vol 18 (1-2) ◽

pp. 8-16

Author(s):

Hakan Kaleağası

Keyword(s):

Autosomal Recessive ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Hereditary Ataxias

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Amino Acid Changes in the Mouse Mutant Dystonia Musculorum Similar to Those in Friedreich’s Ataxia

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100043936 ◽

1982 ◽

Vol 9 (2) ◽

pp. 185-188 ◽

Cited By ~ 15

Author(s):

A. Messer

Keyword(s):

Amino Acid ◽

Experimental Model ◽

Neurological Disorder ◽

Autosomal Recessive ◽

Red Nucleus ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Mouse Mutant ◽

Sensory Afferents ◽

Recessive Mutant

SUMMARY:An autosomal recessive mutant strain of mouse with a progressive neurological disorder is described. Histopathology is dramatic in the sensory afferents and in the red nucleus. In the cerebellar vermis the concentrations of glutamate, aspartate, glycine and GABA are significantly reduced, and in the cerebellar hemispheres the taurine/glutamate ratio is elevated. These mice may provide a useful experimental model of Friedreich’s ataxia.

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Electromyography and Nerve Conduction Studies in Friedreich's Ataxia and Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100119614 ◽

1979 ◽

Vol 6 (2) ◽

pp. 185-189 ◽

Cited By ~ 29

Author(s):

J.P. Bouchard ◽

A. Barbeau ◽

R. Bouchard ◽

R.W. Bouchard

Keyword(s):

Nerve Conduction ◽

Autosomal Recessive ◽

Clinical Signs ◽

Sensory Nerve ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Nerve Conduction Studies ◽

Spastic Ataxia ◽

Group I ◽

Electrophysiological Studies

SummaryTwenty four ataxie patients were investigated with electromyography and nerve conduction studies. They were divided in two groups according to the area they came from, the evolution of the disease, and the clinical signs. Group I patients from the Rimouski area displayed all the clinical and electrophysiological signs of Friedreich's ataxia. Group II comprised patients who presented with a new syndrome known as the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Although the clinical evolution was better in the latter, there were more electromyographic signs of denervation and the motor conduction velocities were slower. Both groups showed identical and important abnormalities in sensory nerve conduction.The results of electrophysiological studies in spastic ataxia have not been reported to our knowledge. They underline the place of spastic ataxia as distinct f rom Friedreich's ataxia, spastic paraplegia, and the known familial neuropathies.

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A Possible Genetic Pattern of Taurine Urinary Excretion in Friedreich’s Ataxia

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100043985 ◽

1982 ◽

Vol 9 (2) ◽

pp. 209-215 ◽

Cited By ~ 6

Author(s):

A. Barbeau ◽

F. Patenaude ◽

G. Nadon ◽

M. Charbonneau ◽

T. Cloutier

Keyword(s):

Urinary Excretion ◽

Autosomal Recessive ◽

Genetic Defect ◽

High Capacity ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Uptake System ◽

Genetic Pattern ◽

Before And After ◽

Normal Controls

SUMMARY:The taurine urinary excretion pattern, before and after an oral load of 250 mg taurine, was studied in normal control subjects and in patients with typical Friedreich’s ataxia. It was demonstrated that in both situations the ataxic patients fell within the sub-types of “intermediate” and “high taurine excretors”, while none were “low taurine excretors”. It was also demonstrated that the excretion of taurine after a load in the obligate heterozygotes parents of the ataxic patients was intermediate between normal controls and patients. It is postulated that patients with Friedreich’s Ataxia lack normal regulation of the high affinity-low capacity uptake system for taurine (the TH system) in the brush border of kidney tubules. The low affinity-high capacity uptake system in the same membranes (the TL system) appears to be normal in Friedreich’s patients. The normal allele could be called THN and the variant THF and this trait would be inherited in an autosomal recessive fashion if it is linked to the Freidreich phenotype. Whether this finding is or is not the basic genetic defect in Friedreich’s Ataxia will require more studies to clarify, but it is of interest to note that a similar pattern appears to be present in the fibroblasts of these patients.

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Computed Tomography of Posterior Fossa in Hereditary Ataxias

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100119638 ◽

1979 ◽

Vol 6 (2) ◽

pp. 195-198 ◽

Cited By ~ 15

Author(s):

R. Langelier ◽

J.P. Bouchard ◽

R.B Ouchard

Keyword(s):

Computed Tomography ◽

Central Nervous System ◽

Nervous System ◽

Posterior Fossa ◽

Autosomal Recessive ◽

Cerebellar Atrophy ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Hereditary Ataxias ◽

The Central Nervous System

SummaryNine cases of Friedreich's ataxia and seven cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) were submitted to neuroradiological procedures to determine the extent of atrophie processes in the central nervous system. All cases had a computerized cerebral tomography and five were studied with pneumencephalo-graphy. The results show a correlation between the two tests and the comparison between Friedreich's ataxia and ARS ACS.In Friedreich's ataxia, the radiological signs are variable and discrete in most of the cases. In A RSA CS there are constant signs of cerebellar atrophy almost limited to the superior parts of the vermis and anterior lobes.

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