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FARAFARA Cure FA

 

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.

 


 

Peripapillary retinal nerve fibre layer thickness in Friedreich's ataxia: a biomarker for trials?

This letter describes data comparing retinal nerve fiber layer thinning measured by optical coherence tomography (OCT) to other clinical measures of FA progression. It shows that OCT measurements correlate to GAA1 length, disease duration, SARA score and activities of daily living scores, offering potential as a biomarker for clinical trials.

Read the entire article HERE

New Insights into the Hepcidin-Ferroportin Axis and Iron Homeostasis in iPSC-Derived Cardiomyocytes from Friedreich's Ataxia Patient

Iron balance in the cardiac tissue as well as the involvement of the hepcidin-ferroportin (HAMP-FPN) axis in this process and in cardiac functionality are not fully understood. Imbalance of iron occurs in several cardiac diseases, including iron-overload cardiomyopathies such as Friedreich's ataxia (FA). Using induced pluripotent stem cells (iPSCs) to create heart cells (cardiomyocytes) from cells from a FRDA patient and of a healthy control subject in order to study the cardiac iron balance and the HAMP-FPN axis. FA cardiomyocytes maintain the FA-like phenotype. They found that FA cardiomyocytes show an increase in the protein expression of hepcidin and ferroportin. Moreover, they found an unexpected nuclear localization of ferroportin in both affected and unaffected cardiomyocytes. However, the amount of the nuclear ferroportin was lower in FA cardiomyocytes than in controls. These and other data suggest that iron handling and the HAMP-FPN axis regulation in FA cardiac cells are hampered and that ferroportin may have new, still not fully understood, functions.

Read the entire article HERE

Hypoxia Rescues Frataxin Loss by Restoring Iron Sulfur Cluster Biogenesis

Mootha lab team Frataxin participates in the biosynthesis of Fe-S clusters and is considered to be essential for viability. This paper reports that when grown in 1% ambient O2, FXN null yeast, human cells, and nematodes are fully viable. In human cells, hypoxia restores steady-state levels of Fe-S clusters and normalizes ATF4, NRF2, and IRP2 signaling events associated with FRDA. Cellular studies and in vitro reconstitution indicate that hypoxia acts through HIF-independent mechanisms that increase bioavailable iron as well as directly activate Fe-S synthesis. In a mouse model of FRDA, breathing 11% O2 attenuates the progression of ataxia, whereas breathing 55% O2 hastens it. This work identifies oxygen as a key environmental variable in the pathogenesis associated with FXN depletion, with important mechanistic and therapeutic implications.

Read the entire article HERE



Download the Q&A PDF HERE

Probing the multifactorial source of hand dysfunction in Friedreich ataxia

Friedreich ataxia (FRDA) has a significant effect on hand function which in turn, may compromise independence and quality of life. This study sought to identify the extent of muscle weakness, spasticity and changes in joint range in the hands of individuals with FRDA. The group found evidence for both upper and lower motor neuron impairment in this population. Thirteen (68.0%) participants had spasticity in the dominant wrist and finger flexors, and seven (36.8%) had contracture in at least one joint of either hand. Sixteen (84.3%) participants demonstrated weakness in the intrinsic musculature of the hands and the majority demonstrated some degree of hyperextension at the metacarpophalangeal joints of either hand. Significant correlations were found between functional independence capacity and clinical parameters, and components of spasticity and weakness in both the dominant and non-dominant hands. Moreover, spasticity and weakness in the dominant hand were shown to be significant predictors of reduced functional independence capacity. This study highlights for the first time the incidence of upper limb spasticity which, in combination with weakness and contracture, suggests a multifactorial source of hand dysfunction in people with FRDA.

Read the entire article HERE

Identification of a novel missense mutation in Friedreich's ataxia -FXNW 168R

Friedreich's ataxia, characterized by decreased expression of frataxin protein, is caused by GAA trinucleotide repeats within intron 1 in 98% of patients. Two percent of patients carry GAA repeats in conjunction with a point mutation. In this work, the authors find that frataxinW168R, a novel disease-causing missense mutation, is expressed predominantly as the intermediate frataxin42-210 form, with very little expression of mature frataxin81-210 form. Its localization to mitochondria is not impaired. Additionally, increasing frataxinW168R precursor levels do not lead to an increase in mature frataxin levels, suggesting these patients will require alternative approaches to repair frataxin processing in order to treat the disorder in a disease-modifying manner.

Read the entire article HERE

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