scholarly journals Generation of transgene-free iPSC lines from three patients with Friedreich’s ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene

2021 ◽  
pp. 102438
Author(s):  
Simge Kelekçi ◽  
Deniz Uğurlu-Çimen ◽  
Deniz Ata ◽  
Burcu Özçimen ◽  
Abdullah Burak Yıldız ◽  
...  
Keyword(s):  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
First Intron

scholarly journals Future Prospects of Gene Therapy for Friedreich’s Ataxia

2021 ◽  
Vol 22 (4) ◽  
pp. 1815 ◽  
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.

scholarly journals Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chiranjeevi Sandi ◽  
Sahar Al-Mahdawi ◽  
Mark A. Pook
Keyword(s):  
Autosomal Recessive ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Therapeutic Option ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Epigenetic Changes ◽  
First Intron ◽  
Challenges And Opportunities ◽  
Transcriptional Reactivation

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by homozygous expansion of a GAA·TTC trinucleotide repeat within the first intron of the FXN gene, leading to reduced FXN transcription and decreased levels of frataxin protein. Recent advances in FRDA research have revealed the presence of several epigenetic modifications that are either directly or indirectly involved in this FXN gene silencing. Although epigenetic marks may be inherited from one generation to the next, modifications of DNA and histones can be reversed, indicating that they are suitable targets for epigenetic-based therapy. Unlike other trinucleotide repeat disorders, such as Huntington disease, the large expansions of GAA·TTC repeats in FRDA do not produce a change in the frataxin amino acid sequence, but they produce reduced levels of normal frataxin. Therefore, transcriptional reactivation of the FXN gene provides a good therapeutic option. The present paper will initially focus on the epigenetic changes seen in FRDA patients and their role in the silencing of FXN gene and will be concluded by considering the potential epigenetic therapies.

scholarly journals Friedreich's Ataxia, Frataxin, PIP5K1B: Echo of a Distant Fracas

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Aurélien Bayot ◽  
Pierre Rustin
Keyword(s):  
Candidate Gene ◽  
Recent Observation ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
The Other ◽  
First Intron ◽  
Other Hand ◽  
Encoding Gene ◽  
Instrumental Role

“Frataxin fracas” were the words used when referring to the frataxin-encoding gene (FXN) burst in as a motive to disqualify an alternative candidate gene,PIP5K1B, as an actor in Friedreich's ataxia (FRDA) (Campuzano et al., 1996; Cossee et al., 1997; Carvajal et al., 1996). The instrumental role in the disease of large triplet expansions in the first intron ofFXNhas been thereafter fully confirmed, and this no longer suffers any dispute (Koeppen, 2011). On the other hand, a recent study suggests that the consequences of these large expansions inFXNare wider than previously thought and that the expression of surrounding genes, includingPIP5K1B, could be concurrently modulated by these large expansions (Bayot et al., 2013). This recent observation raises a number of important and yet unanswered questions for scientists and clinicians working on FRDA; these questions are the substratum of this paper.

Otoneurological Findings in Friedreich's Ataxia and Other Inherited Neuropathies

1986 ◽  
Vol 25 (2) ◽  
pp. 84-91 ◽  
Author(s):  
E. Cassandro ◽  
F. Mosca ◽  
L. Sequino ◽  
F. A. De Falco ◽  
G. Campanella
Keyword(s):  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Inherited Neuropathies

scholarly journals Echocardiographic Findings in Friedreich's Ataxia

1976 ◽  
Vol 3 (4) ◽  
pp. 329-332 ◽  
Author(s):  
H.F. Gattiker ◽  
A. Davignon ◽  
A. Bozio ◽  
J. Batlle-Diaz ◽  
G. Geoffroy ◽  
...  
Keyword(s):  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
Ventricular Free Wall ◽  
Slight Reduction ◽  
Free Wall ◽  
Left Ventricular Free Wall ◽  
Echocardiographic Examination ◽  
Septal Hypertrophy ◽  
Echocardiographic Findings

SUMMARY:Echocardiographic examination of 21 patients with Friedreich's ataxia (age 7 to 28 years) showed cardiac abnormalities in 90% of the cases. They were characterized by varying degrees of septal hypertrophy in 81%, left ventricular free wall hypertrophy in 61%, and a slight reduction of left ventricular internal dimension in 57% of the cases. Asymmetric septal hypertrophy (ASH) with a septal/left ventricular free wall ratio of over 1.3 was found in 29% of the cases, and systolic anterior motion (SAM) of the mitral valve in three patients. Two other patients showed evidence of a different type of cardiomyopathy with marked symmetric left ventricular hypertrophy and marked left ventricular enlargement.

Square Wave Jerks in Friedreich's Ataxia

1978 ◽  
Vol 85 (3) ◽  
pp. 400-406 ◽  
Author(s):  
Robert T. Dale ◽  
Albert W. Kirby ◽  
Robert S. Jampel
Keyword(s):  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Square Wave
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