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FARAFARA Cure FA

 

Scientific News

FARA funds research progress

In this section, you will find the most recent FA research publications, many of which are funded by FARA, as well as information on upcoming conferences and symposiums. You can search for articles by date using the archive box in the right hand column. To locate FARA Funded or Supported Research, click the hyperlink in the right hand column. You may also search for specific content using key words or phrases in the search button at the top right of your screen. Please be sure to visit other key research sections of our website for information on FARA’s Grant Program and the Treatment Pipeline.

 


 

FAST-1 antisense RNA epigenetically alters FXN expression

Friedreich ataxia (FRDA) is a multisystem genetic disorder caused by GAA repeat expansion mutations within the FXN gene, resulting in heterochromatin formation and deficiency of frataxin protein. Elevated levels of the FXN antisense transcript (FAST-1) have previously been detected in FRDA. To investigate the effects of FAST-1 on the FXN gene expression, this group looked at effects of FAST-1 in non-FRDA cell lines and in FRDA fibroblast cells. They observed decreased FXN expression in each FAST-1 overexpressing cell type compared to control cells and found that FAST-1 overexpression is associated with both CCCTC-Binding Factor (CTCF) depletion and heterochromatin formation at the 5'UTR of the FXN gene. Knocking down FAST-1 in FRDA cells significantly increased FXN expression. The effects of FAST-1 expression on the FXN locus suggest a direct role for FAST-1 in the FRDA molecular disease mechanism and support the hypothesis that inhibition of FAST-1 may be a potential approach for FRDA therapy.

Read the entire article HERE

Characterization of a new N-terminally acetylated extra-mitochondrial isoform of frataxin in human erythrocytes

Frataxin is a highly conserved protein encoded by the frataxin (FXN) gene. The full-length 210-amino acid form of protein frataxin (1-210; isoform A) expressed in the cytosol of cells rapidly gets moved to the mitochondria, where it is converted to the mature form (81-210). Mature frataxin (81-210) is a critically important protein because it facilitates the assembly of mitochondrial iron-sulfur cluster protein complexes such as aconitase, lipoate synthase, and succinate dehydrogenases. Decreased expression of frataxin protein is responsible for Friedreich's ataxia. The mitochondrial form of frataxin has long been thought to be present in red blood cells even though they lack mitochondria. This paper shows that frataxin in red blood cells is a novel form of frataxin (called isoform E) with 135-amino acids and an N-terminally acetylated methionine residue. There is three times more isoform E in red blood cells from the whole blood of healthy volunteers compared to the mature mitochondrial frataxin present in other blood cells. Isoform E lacks a mitochondrial targeting sequence and so is distributed to both cytosol and the nucleus when expressed in cultured cells. When extra-mitochondrial frataxin isoform E is expressed in HEK 293 cells, it is converted to a shorter isoform identical to the mature frataxin found in mitochondria, which raises the possibility that it is involved in disease etiology. The ability to specifically quantify extra-mitochondrial and mitochondrial isoforms of frataxin in whole blood will make it possible to readily follow the natural history of diseases such as Friedreich's ataxia and monitor the efficacy of therapeutic interventions.

Read the entire article HERE

Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia

Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy.

Read the entire article HERE

Oligonucleotides Hold Promise as a Therapy for Friedreich's Ataxia

Friedreich's ataxia currently is incurable, but synthetic antisense oligonucleotides have demonstrated promising results in increasing frataxin gene expression and restoring it to normal levels

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Voyager Therapeutics Announces Additional Data at the American Society of Gene and Cell Therapy 2018 Annual Meeting

CAMBRIDGE, Mass., May 18, 2018 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (NASDAQ:VYGR), a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases today announced additional data presentations at the American Society of Gene and Cell Therapy (ASGCT) taking place May 16-19, 2018, in Chicago, Ill. This evening at ASGCT, Voyager presented results for its gene therapy program for Friedreich’s ataxia as well as data related to Voyager’s novel adeno-associated virus (AAV) capsid optimization efforts.

Read the entire article HERE

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