It has been established for a long time that frataxin takes part in two important metabolic pathways related to iron, an element that is at the same time essential for life but also insoluble and toxic. It has been thought that frataxin acts as an iron chaperone, a substance which carries iron, and that it is involved with the formation of iron-sulphur clusters. These are necessary for the functioning of the mitochondria and thus for energy production in the cell.
Annalisa Pastore, in NIMR's Division of Molecular Structure, has shown that frataxin is not just a chaperone but an inhibitor of the iron-sulphur cluster formation process. It regulates the formation of such clusters to match the number of available acceptors, in response to the concentration of iron. Friedreich's ataxia patients, who have only reduced quantities of frataxin, therefore lack this important regulatory process. Without it, too many iron-sulphur clusters are formed and, being unstable species, they decompose. This causes the accumulation of insoluble iron which precipitates in the cell, as is observed in the tissues of FA patients. This in turn causes metabolic damage that leads to cell death.
Dr Pastore said:
"Frataxin is known to function in the mitochondria, the energy-producing factories of the cell, but until now we did not know how frataxin worked. Our research allows us a completely new perspective into understanding Friedreich's Ataxia which will hopefully help us find a cure for this debilitating disease".
Julie Greenfield from Ataxia UK, the support organisation for people with Friedreich's ataxia, welcomed these findings and said:
"This research will further our understanding of the disease mechanism and provide useful information for the development of treatments."
Friedreich's ataxia is a genetic disorder which affects about one individual per 50,000 in the UK. It is a debilitating, life-shortening, degenerative neuro-muscular disorder. It is associated with the loss of coordination (ataxia) in the limbs, increased incidence of diabetes, and hypertrophic cardiomyopathy, which is a serious heart condition.
Symptoms can be observed from childhood or in young adulthood. Childhood onset of FA is usually between the ages of five and fifteen and tends to be associated with a more rapid progression. The mental capabilities of people with Friedreich's ataxia remain completely intact until the later stages. There are currently no treatments for FA.
Original article
The research findings are published in full in:
Salvatore Adinolfi, Clara Iannuzzi, Filippo Prischi, Chiara Pastore, Stefania Iametti, Stephen R Martin, Franco Bonomi and Annalisa Pastore (2009)
Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS
Nature Structural and Molecular Biology Epub ahead of print. Publisher abstract
Internal links
Annalisa Pastore's research group
External links
News item on MRC website
[7 April 2009]
Article kindly supplied by MariLuz González Casas
Link to the article:




The legacy of Marie Schlau: literature to help cure Friedreich's Ataxia

If you feel like reading an unputdownable novel while collaborating with a just and solidary cause, "The Legacy of Marie Schlau" is your book! 100% of all funds raised will be dedicated to medical research to find a cure for Friedreich's Ataxia, a neurodegenerative disease that affects mostly young people, shortening their life expectancy and confining them to a wheelchair.

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Research projects currently being financed by BabelFAmily

Currently, BabelFAmily is financing two promising research projects aimed at finding a cure for Friedreich's Ataxia. Whenever you make a donation to us or purchase a copy of "The legacy of Marie Schlau", this is where all funds raised will be devoted to:

1) Gene Therapy for Friedreich's Ataxia research project:

The project is the result of an initiative of Spanish people affected by this rare disease who are grouped in GENEFA in collaboration with the Spanish Federation of Ataxias and the BabelFAmily. The Friedreich’s Ataxia Research Alliance (FARA), one of the main patients’ associations in the United States now joins the endeavour.

2) Frataxin delivery research project:
The associations of patients and families Babel Family and the Asociación Granadina de la Ataxia de Friedreich (ASOGAF) channel 80,000 euros of their donations (50% from each organisation) into a new 18-month project at the Institute for Research in Biomedicine (IRB Barcelona). The project specifically aims to complete a step necessary in order to move towards a future frataxin replacement therapy for the brain, where the reduction of this protein causes the most damage in patients with Friedreich’s Ataxia.

The study is headed by Ernest Giralt, head of the Peptides and Proteins Lab, who has many years of experience and is a recognised expert in peptide chemistry and new systems of through which to delivery drugs to the brain, such as peptide shuttles—molecules that have the capacity to carry the drug across the barrier that surrounds and protects the brain. Since the lab started its relation with these patients’ associations in 2013*, it has been developing another two projects into Friedrich’s Ataxia.



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