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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.



RNA-DNA hybrids promote the expansion of Friedreich's ataxia (GAA)n repeats via break-induced replication

Expansion of simple DNA repeats is responsible for numerous hereditary diseases in humans. The role of DNA replication, repair and transcription in the expansion process has been well documented. Here we analyzed, in a yeast experimental system, the role of RNA-DNA hybrids in genetic instability of long (GAA)n repeats, which cause Friedreich's ataxia. Knocking out both yeast RNase H enzymes, which counteract the formation of RNA-DNA hybrids, increased (GAA)n repeat expansion and contraction rates when the repetitive sequence was transcribed. Unexpectedly, we observed a similar increase in repeat instability in RNase H-deficient cells when we either changed the direction of transcription-replication collisions, or flipped the repeat sequence such that the (UUC)n run occurred in the transcript. The increase in repeat expansions in RNase H-deficient strains was dependent on Rad52 and Pol32 proteins, suggesting that break-induced replication (BIR) is responsible for this effect. We conclude that expansions of (GAA)n repeats are induced by the formation of RNA-DNA hybrids that trigger BIR. Since this stimulation is independent of which strand of the repeat (homopurine or homopyrimidine) is in the RNA transcript, we hypothesize that triplex H-DNA structures stabilized by an RNA-DNA hybrid (H-loops), rather than conventional R-loops, could be responsible.

Read the entire article HERE

Serum uric acid in Friedreich Ataxia

Serum uric acid (UA) is a circulating antioxidant whose levels are typically lower in patients with neurodegenerative diseases than in unaffected individuals, reflecting a higher oxidative stress.These investigators looked at serum UA in Friedreich Ataxia (FRDA), in order to explore novel disease biomarkers. Serum UA was measured in 19 FRDA patients and compared to 26 unaffected individuals. Serum UA levels were significantly higher in FRDA than in unaffected individuals (p = .016), independent of age, gender and BMI. No correlations emerged with clinical data. Contrary to other neurodegenerative diseases, in FRDA, we observed an independent increase of serum UA content. We speculate that this may result from biochemical impairment induced by the genetic defect, acting as a sort of compensatory antioxidant defense, although proper dedicated studies are mandatory. This preliminary report suggests UA as a potential biomarker for FRDA and encourages further studies on novel therapeutic strategies.

Read the entire article HERE

Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting the Mutant Expanded Repeat

Friedreich's Ataxia (FA) is an inherited neurologic disorder caused by an expanded GAA repeat within intron 1 of the frataxin (FXN) gene that reduces expression of FXN protein. Agents that increase expression of FXN have the potential to alleviate the disease. We previously reported that duplex RNAs (dsRNAs) and antisense oligonucleotides (ASOs) complementary to the GAA repeat could enhance expression of FXN protein. We now explore the potential of a diverse group of chemically modified dsRNAs and ASOs to define the breadth of repeat-targeted synthetic nucleic acids as a platform for therapeutic development for FA. ASOs and dsRNAs can activate FXN protein expression in FA patient-derived cell lines that possess varied numbers of GAA repeats. Increased FXN protein expression was achieved by ASOs incorporating diverse chemical modifications with low nanomolar potencies, suggesting substantial flexibility in choosing compounds for further chemical optimization and animal studies. Our data encourage further development of ASOs as agents to treat FA.

Read the entire article HERE

Join Reata WebEx. Get updates on the MOXIe Phase 2 Study

Please join Jennifer Farmer, Executive Director, FARA & Dr. Keith Ward, Chief Development Officer of Reata Pharmaceuticals, for one of two upcoming meetings to discuss the MOXIe clinical trial in more detail.

The purpose of the WebEx is to discuss and review Part 1 MOXIe data and provide updates to the ongoing Part 2 portion of the study to the patient community, including study participation, eligibility criteria, how to enroll, study status, FAQs, etc. The WebEx meetings will include time at the end for FARA/Reata to answer questions from the participants.

Reata is evaluating the safety and effectiveness of an investigational medication, RTA 408 (omaveloxolone), in Friedreich’s ataxia.

Meeting Dates and Times
There will be two meetings. The same information will be presented at both meetings, so pick the time that best fits your schedule. They will be recorded so you can listen to them later if you are unable to attend one live.

  • Wednesday, January 31st at 9:00am PST/12:00pm EST
  • Thursday, February 1st at 5:00pm PST/8:00pm EST

Target Audience
This event is aimed at any interested individuals affected by Friedreich’s ataxia and/or family members or caregivers.

What is a Webex Meeting?
A Webex is an online meeting that includes audio and screen sharing. All you need is an internet connection!

How to Participate
To register for one of the online Webex meetings, please contact Hanh Nguyen at Then simply follow the link provided at the appropriate time. In order to receive the link to join the Webex meeting, you must register in advance.

Quantitative proteomics in Friedreich's ataxia B-lymphocytes: A valuable approach to decipher the biochemical events responsible for pathogenesis

Friedreich's ataxia (FRDA) represents the most frequent type of autosomal-recessively inherited ataxia and is caused by the deficiency of frataxin, a mitochondrial protein. It is known that frataxin-deficiency leads to alterations in cellular and mitochondrial iron metabolism and impacts in the cell physiology at several levels. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. Currently, cellular antioxidant defense is dysregulated when frataxin is deficient, which exacerbates oxidative damage in FRDA. Moreover, alterations in lipid metabolism have been observed in several models of the disease. To better understand the biochemical sequelae of frataxin reduction, global protein expression analysis was performed using quantitative proteomic experiments in Friedreich's ataxia patient-derived B-lymphocytes as compared to controls. The group confirmed a subset of changes in these cells and importantly, observed previously unreported signatures of protein expression. Among the novel protein signatures identified, the decrease in CHCHD4 might partly explain some aspects of the molecular pathogenesis of FRDA. The identification of a core set of proteins changing in the FRDA pathogenesis is a useful tool in trying to decipher the function(s) of frataxin in order to clarify the mitochondrial metabolic disease process.

Read the entire article HERE

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