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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.


Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia

Friedreich ataxia (FA) is a progressive neurodegenerative disease caused by expansion of a trinucleotide repeat within the first intron of the gene that encodes frataxin. In our study, we investigated the regulation of frataxin expression by iron and demonstrated that frataxin mRNA levels decrease significantly in multiple human cell lines treated with the iron chelator, desferal (DFO). In addition, frataxin mRNA and protein levels decrease in fibroblast and lymphoblast cells derived from both normal controls and from patients with FA when treated with DFO. Lymphoblasts and fibroblasts of FA patients have evidence of cytosolic iron depletion, as indicated by increased levels of iron regulatory protein 2 (IRP2) and/or increased IRE-binding activity of IRP1. We postulate that this inferred cytosolic iron depletion occurs as frataxin-deficient cells overload their mitochondria with iron, a downstream regulatory effect that has been observed previously when mitochondrial iron-sulfur cluster assembly is disrupted.

Read More: Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia

Antioxidant use in Friedreich ataxia

Many antioxidants have been suggested as potential treatments for Friedreich ataxia, but have not been tested in clinical trials. We found that a majority of patients in our cohort already use such antioxidants, including idebenone, which is not available at a pharmaceutical grade in the United States. Younger age, cardiomyopathy and shorter GAA repeat length were independent predictors of idebenone use, but no factors predicted use of other antioxidants. This confirms that non-prescription antioxidant use represents a major confounder to formal trials of existing and novel agents for Friedreich ataxia.

Read More: Antioxidant use in Friedreich ataxia

HDAC Inhibitors Correct Frataxin Deficiency in a Friedreich Ataxia Mouse Model

Friedreich ataxia, an autosomal recessive neurodegenerative and cardiac disease, is caused by abnormally low levels of frataxin, an essential mitochondrial protein. All Friedreich ataxia patients carry a GAA⋅TTC repeat expansion in the first intron of the frataxin gene, either in the homozygous state or in compound heterozygosity with other loss-of-function mutations. The GAA expansion inhibits frataxin expression through a heterochromatin-mediated repression mechanism. Histone modifications that are characteristic of silenced genes in heterochromatic regions occur at expanded alleles in cells from Friedreich ataxia patients, including increased trimethylation of histone H3 at lysine 9 and hypoacetylation of histones H3 and H4.

Read More: HDAC Inhibitors Correct Frataxin Deficiency in a Friedreich Ataxia Mouse Model

Structural basis of the iron storage function of frataxin from single-particle reconstruction of the iron-loaded oligomer

The mitochondrial protein frataxin plays a central role in mitochondrial iron homeostasis, and frataxin deficiency is responsible for Friedreich ataxia, a neurodegenerative and cardiac disease that affects 1 in 40000 children. Here we present a single-particle reconstruction from cryoelectron microscopic images of iron-loaded 24-subunit oligomeric frataxin particles at 13 and 17 Å resolution. Computer-aided classification of particle images showed heterogeneity in particle size, which was hypothesized to result from gradual accumulation of iron within the core structure. Thus, two reconstructions were created from two classes of particles with iron cores of different sizes. The reconstructions show the iron core of frataxin for the first time.

Read More: Structural basis of the iron storage function of frataxin from single-particle reconstruction ...

Orthopedic shoes improve gait in Friedreich's ataxia: a clinical and quantified case study

Our aim was to evaluate with modern tools the efficacy of orthopedic shoes on gait disorders in Friedreich's ataxia. The case of a 26-year-old woman with Friedreich's ataxia is described. She mainly complained of fatigability, ankle instability, frequent falls and pain. Impairments involved a cerebellar syndrome, a proprioceptive deficit, an upper motor neurone syndrome and osteoarticular deformities. Gait disabilities included ataxia and requirement of a cane. Handicap concerned outings, altering quality of life. Orthopedic shoes combined with physical therapy were prescribed. Assessment of treatment was planned after one month. Self-assessment by the patient was noted. Clinical assessment was provided by physical examination and clinical gait analysis supported by video. Quantified assessment was performed with a Gaitrite system recording spatiotemporal gait parameters.

Read More: Orthopedic shoes improve gait in Friedreich's ataxia: a clinical and quantified case study

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