Progression of Friedreich ataxia: quantitative characterization over 5 years.

Objective: Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes and changes to identify predictors of progression and generate power calculations for clinical trials.

Methods: Eight hundred and twelve subjects in a natural history study were evaluated annually across 12 sites using the Friedreich Ataxia Rating Scale (FARS), 9-Hole Peg Test, Timed 25-Foot Walk, visual acuity tests, self-reported surveys and disability scales.

Establishment and Maintenance of Primary Fibroblast Repositories for Rare Diseases-Friedreich's Ataxia Example.

Friedreich's ataxia (FRDA) represents a rare neurodegenerative disease caused by expansion of GAA trinucleotide repeats in the first intron of the FXN gene. The number of GAA repeats in FRDA patients varies from approximately 60 to <1000 and is tightly correlated with age of onset and severity of the disease symptoms. The heterogeneity of Friedreich's ataxia stresses the need for a large cohort of patient samples to conduct studies addressing the mechanism of disease pathogenesis or evaluate novel therapeutic candidates.

IFN-γ for Friedreich ataxia: present evidence.

IFN-γ-1b is currently US FDA approved as an orphan drug for the treatment of chronic granulomatous disease and severe malignant osteopetrosis. It is administered via subcutaneous injection and is a potential therapy for Friedreich ataxia (FRDA), a rare degenerative neurological condition. Ongoing Phase II and III trials in both adults and children with FRDA were preceded by a small Phase I, open-label trial in children that showed that IFN-γ-1b was reasonably well-tolerated and improved overall neurological function as measured by the Friedreich Ataxia Rating Scale after 12 weeks of treatment, though the primary outcome measure of frataxin level showed no improvement.

Expanded GAA repeats impede transcription elongation through the FXN gene and induce transcriptional silencing that is restricted to the FXN locus.

Friedreich's ataxia (FRDA) is a severe neurodegenerative disease caused by homozygous expansion of the guanine-adenine-adenine (GAA) repeats in intron 1 of the FXN gene leading to transcriptional repression of frataxin expression. Post-translational histone modifications that typify heterochromatin are enriched in the vicinity of the repeats, whereas active chromatin marks in this region are underrepresented in FRDA samples. Yet, the immediate effect of the expanded repeats on transcription progression through FXN and their long-range effect on the surrounding genomic context are two critical questions that remain unanswered in the molecular pathogenesis of FRDA.

Frataxin levels in peripheral tissue in Friedreich ataxia.

Objective: Friedreich ataxia (FRDA) is an autosomal recessive ataxia resulting from mutations in the frataxin gene (FXN). Such mutations, usually expanded guanine-adenine-adenine (GAA) repeats, give rise to decreased levels of frataxin protein in both affected and unaffected tissues. The goal was to understand the relationship of frataxin levels in peripheral tissues to disease status.

Analysis of the visual system in Friedreich ataxia.

To use optical coherence tomography (OCT) and contrast letter acuity to characterize vision loss in Friedreich ataxia (FRDA). High- and low-contrast letter acuity and neurological measures were assessed in 507 patients with FRDA. In addition, OCT was performed on 63 FRDA patients to evaluate retinal nerve fiber layer (RNFL) and macular thickness.

Friedreich ataxia clinical outcome measures: natural history evaluation in 410 participants.

Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia, dysarthria, and areflexia. The authors report the progress of a large international noninterventional cohort (n = 410), tracking the natural history of disease progression using the neurologic examination-based Friedreich Ataxia Rating Scale. The authors analyzed the rate of progression with cross-sectional analysis and longitudinal analysis over a 2-year period.

Clinical monitoring in a patient with Friedreich ataxia and osteogenic sarcoma.

Friedreich ataxia is an autosomal recessive neurodegenerative disorder caused by mutations in the FXN gene that result in abnormally low levels of the mitochondrial protein frataxin. The authors recently used a lateral flow immunoassay to measure frataxin levels in a large cohort of controls, carriers, and patients with the condition. The findings show that frataxin levels do not appreciably change over time and correlate well with GAA(1) repeat length and age of onset; thus, frataxin is a reliable and stable marker for severity of disease.

Cardiac dysfunction exacerbated by endocrinopathies in Friedreich ataxia: a case series.

Friedreich ataxia is a neurodegenerative disease characterized by gait abnormalities, cardiomyopathy, and diabetes. Congestive heart failure was recently reported as the most frequent cause of Friedreich ataxia mortality. Cardiac dysfunction is suspected to result from a frataxin deficiency that leads to oxidative damage in cardiac tissues and possible metabolic syndrome characteristics.

Structural and functional profile of the carbohydrate esterase gene complement in Phytophthora infestans.

The plant cell cuticle is the first obstacle for penetration of the host by plant pathogens. To breach this barrier, most pathogenic fungi employ a complex assortment of cell wall-degrading enzymes including carbohydrate esterases, glycoside hydrolases, and polysaccharide lyases. We characterized the full complement of carbohydrate esterase-coding genes in three Phytophthora species and analyzed the expression of cutinase in vitro and in planta; we also determined the cutinase allele distribution in multiple isolates of P.

Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans.

Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement.