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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.

Idebenone treatment in paediatric and adult patients with Friedreich ataxia: long-term follow-up

Antioxidant therapy is a new therapeutical approach for patients with Friedreich ataxia.

To assess the effectiveness of long-term idebenone treatment in Friedreich ataxia patients.

An open-labelled prospective study. Ten paediatric patients (age range 8-18 years) and 14 adults (age range 18-46 years) with genetic diagnosis of Friedreich ataxia were treated with idebenone (5-20mg/kg/day) for 3-5 years. Neurological evolution was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), and cardiological outcomes using echocardiography.

In paediatric patients, no significant differences were observed in ICARS scores and echocardiographic measurements when comparing baseline status and after 5 years of follow-up. Concerning adult cases, ICARS scores showed a significant increase in neurological dysfunctions during 3 years of therapy (Wilcoxon test, p=0.005), while echocardiographic measurements remained unchanged.

Our results indicate that longer-term idebenone treatment prevented progression of cardiomyopathy in both paediatric and adult patients, whereas its stabilizing effect on neurological dysfunction was present only in the paediatric population, mainly before puberty. This suggests that the age at which idebenone treatment is initiated may be an important factor in the effectiveness of the therapy.

Read More: Idebenone treatment in paediatric and adult patients with Friedreich ataxia: long-term follow-up

DNA triplexes and Friedreich ataxia

Friedreich ataxia, the most common inherited ataxia, is caused by the transcriptional silencing of the FXN gene, which codes for the 210 amino acid frataxin, a mitochondrial protein involved in iron-sulfur cluster biosynthesis. The expansion of the GAA x TTC tract in intron 1 to as many as 1700 repeats elicits the transcriptional silencing by the formation of non-B DNA structures (triplexes or sticky DNA), the formation of a persistent DNA x RNA hybrid, or heterochromatin formation. The triplex (sticky DNA) adopted by the long repeat sequence also elicits profound mutagenic, genetic instability, and recombination behaviors. Early stage therapeutic investigations involving polyamides or histone deacetylase inhibitors are being pursued. Friedreich ataxia may be one of the most thoroughly studied hereditary neurological disease from a pathophysiological standpoint.

Read More: DNA triplexes and Friedreich ataxia

Hydrogen peroxide scavenging rescues frataxin deficiency in a Drosophila model of Friedreich's ataxia

Friedreich's ataxia (FRDA) is a neurodegenerative disorder arising from a deficit of the mitochondrial iron chaperone, frataxin. Evidence primarily from yeast and mammalian cells is consistent with the hypothesis that a toxic hydroxyl radical generated from hydrogen peroxide (H2O2) via iron-catalyzed Fenton chemistry at least partially underlies the pathology associated with this disease. However, no whole-organism studies have been presented that directly test this hypothesis. We recently developed a Drosophila model that recapitulates the principal hallmarks of FRDA [Anderson PR, Kirby K, Hilliker A, Phillips JP (2005) Hum Mol Genet 14:3397-3405]. Using the Drosophila FRDA model, we now report that ectopic expression of enzymes that scavenge H2O2 suppresses the deleterious phenotypes associated with frataxin deficiency.

Read More: Hydrogen peroxide scavenging rescues frataxin deficiency...

Call for Patients with Friedreich’s Ataxia

We are pleased to be able to announce today that Santhera Pharmaceuticals is now recruiting patients with Friedreich’s Ataxia in the United States, for a Phase III clinical research trial looking at the effects of idebenone on the nervous system and the heart.

We are looking for patients between the ages of 8 and 17 years who have been diagnosed with Friedreich’s Ataxia.

To participate, you must be able to.

  • Walk at least 33 feet without accompanying person
  • Not have participated in the Phase II idebenone study sponsored by the NIH

About the study

  • Participation in the study is for 9 months; 6 of those months you will be treated
  • with study medication or placebo (an inactive pill with no drug in it)
  • There are 3 possible treatments: 2 different doses of idebenone or a placebo
  • There are 5 visits to the hospital
    • Travel costs are fully paid for, including hotel

Read More: Call for Patients with Friedreich’s Ataxia

Targeting the gene in Friedreich Ataxia

Pathological expansions of GAA repeats in the first intron of the frataxin gene cause most cases of Friedreich ataxia, a progressively debilitating neurodegenerative disease. The disease is inherited in an autosomal recessive manner and the GAA repeats are suspected to form unusual non B-DNA conformations that decrease transcription and subsequently reduce levels of the encoded protein, frataxin. Recent work has shown that GAA repeats induce heterochromatin formation and silencing of the frataxin gene locus. Frataxin plays a crucial role in iron metabolism and detoxification and interacts with electron transport chain proteins. Clinical trials are currently underway to examine the efficacy of antioxidants in the treatment of Friedreich ataxia, but therapeutics designed to  increase frataxin message levels are still in the developmental stages. This review will focus on the progress of potential treatment strategies for Friedreich ataxia that target the GAA expanded gene and seek to increase the level of frataxin message and protein.

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