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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.


Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability

In somatic tissues of Friedreich's ataxia (FRDA) patients, (GAA)n repeat tracts are highly unstable, with contractions more common than expansions. The authors describe an experimental system to characterize GAA repeat contractions in yeast and to conduct a genetic analysis of this process. The study found that large-scale contraction is a one-step process, resulting in a median loss of ∼60 triplet repeats. This genetic analysis revealed that contractions occur during DNA replication, rather than by various DNA repair pathways. Repeats contract in the course of lagging-strand synthesis: The processivity subunit of DNA polymerase δ, Pol32, and the catalytic domain of Rev1, a translesion polymerase, act together in the same pathway to counteract contractions. Accumulation of single-stranded DNA (ssDNA) in the lagging-strand template greatly increases the probability that (GAA)n repeats contract, which in turn promotes repeat instability in rfa1, rad27, and dna2 mutants. Finally, by comparing contraction rates for homopurine-homopyrimidine repeats differing in their mirror symmetry, we found that contractions depend on a repeat's triplex-forming ability. The authors propose that accumulation of ssDNA in the lagging-strand template fosters the formation of a triplex between the nascent and fold-back template strands of the repeat. Occasional jumps of DNA polymerase through this triplex hurdle, result in repeat contractions in the nascent lagging strand.

Read the entire article HERE

MDA Awards Venture Philanthropy Funding of More Than $1M to AavantiBio to Develop Gene-Targeting Therapy for Friedreich's Ataxia

NEW YORK and GAINESVILLE, Fla., Jan. 13, 2020 -- The Muscular Dystrophy Association (MDA) and AavantiBio, a biotechnology company developing a gene-targeting therapy for Friedreich's ataxia (FA), today announced the award of MDA Venture Philanthropy (MVP) funding totaling $1,076,232 to advance AavantiBio's phase 2 clinical trial of a gene-replacement therapy for the disease. MVP is MDA's drug development program, which is exclusively focused on funding the discovery and clinical application of treatments and cures for neuromuscular disorders. MVP evaluates and makes targeted investments in for-profit and not-for-profit companies and academics developing therapeutics.

Read the entire Press Release HERE

Mammalian iron-sulfur cluster biogenesis: Recent insights into the roles of frataxin, acyl carrier protein and ATPase-mediated transfer to recipient proteins.

The recently solved crystal structures of the human cysteine desulfurase NFS1, in complex with the LYR protein ISD11, the acyl carrier protein ACP, and the main scaffold ISCU, have shed light on the molecular interactions that govern initial cluster assembly on ISCU. In this review, the authors aim to highlight recent insights into iron-sulfur (Fe-S) cluster (ISC) biogenesis in mammalian cells that have arisen from the crystal structures of the core ISC assembly complex. The authors will also discuss how ISCs are delivered to recipient proteins and the challenges that remain in dissecting the pathways that deliver clusters to numerous Fe-S recipient proteins in both the mitochondrial matrix and cytosolic compartments of mammalian cells.

Read the entire article HERE

Retrotope Expands its Drug Pipeline with the First Dosing of RT001 in patients with Friedreich’s ataxia (FA)

Three clinical trials centers now open for enrollment; two additional ones initiating

LOS ALTOS, Calif., January 9, 2020 -- Retrotope announced today that it has dosed its first patient in a Phase 2/3 clinical trial of RT001 in Friedreich’s ataxia, the most common of the inherited ataxias. RT001, a stabilized fatty acid drug, has been shown to reduce lipid peroxidation leading to cell death in patients across a wide swath of degenerative diseases, including FA. More information and a list of participating clinical sites for the current trial in FA can be obtained at ClinicalTrials.gov http://bit.ly/2T2FWA5. With this trial, the company expands its pipeline of indications for RT001 which is currently being studied in a pivotal trial in another fatal, neurodegenerative disease, Infantile Neuroaxonal Dystrophy (INAD), which is fully enrolled.

View the entire Press Release HERE

Longitudinal Increases in Cerebral Brain Activation During Working Memory Performance in Friedreich Ataxia: 24-Month Data from IMAGE-FRDA

This study assessed longitudinal changes in brain activation, associated with working memory performance (N-back task), and grey matter volume over 24 months in 21 individuals with Friedreich Ataxia (FRDA) and 28 healthy controls using functional and structural magnetic resonance imaging, respectively. Participants also completed a neurocognitive battery assessing working memory (digit span), executive function (Stroop, Haylings), and set-shifting (Trail Making Test). Individuals with FRDA displayed significantly increased brain activation over 24 months in ventral attention brain regions, including bilateral insula and inferior frontal gyrus (pars triangularis and pars opercularis), compared with controls, but there was no difference in working memory (N-back) performance between groups. Moreover, there were no significant differences in grey matter volume changes between groups. Significant correlations between brain activations and both clinical severity and age at disease onset were observed in FRDA individuals only at 24 months. There was significant longitudinal decline in Trail Making Test (TMT) difference score (B-A) in individuals with FRDA, compared with controls. These findings provide the first evidence of increased longitudinal activation over time in the cerebral cortex in FRDA, compared with controls, despite comparable working memory performance. This finding represents a possible compensatory response in the ventral attention network to help sustain working memory performance in individuals with FRDA.

Read the entire article HERE

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