The defective gene responsible for Friedreich's ataxia was identified over 20 years ago, but so far our ideas of how this gene causes the disease have been merely speculative. It was assumed that, as a result of the mutation, the gene could no longer be transcribed because this stretch of DNA was inaccessible. FMI Group Leader Marc Bühler and his team have now carried out experiments demonstrating that this is not the case and revealing what actually happens in Friedreich's ataxia.
Friedreich's ataxia is caused by a deficiency of the protein frataxin. Frataxin is essential for iron metabolism in mitochondria - the cellular components responsible for energy production. Accordingly, mitochondria are especially important in cells with substantial energy requirements, such as nerve cells or heart muscle. It is therefore not surprising that these cells are particularly affected in Friedreich's ataxia: patients with this condition experience degeneration of the large sensory neurons and spinocerebellar tracts, but also cardiomyopathy.
In patients with Friedreich's ataxia, a nucleotide sequence in the gene coding for frataxin is repeated up to 1000 times, compared with only about 30 times in healthy individuals. The FMI researchers were able to confirm that, owing to this expanded repeat tract, the gene is not correctly transcribed. Specifically, they showed that transcription of the gene into messenger RNA (mRNA) is blocked at the elongation step. As a result, transcription of the gene is prematurely terminated and the protein is not synthesized. In contrast to the current view that densely packed chromatin causes silencing of the gene, the researchers showed that the repetitive DNA on its own already constitutes on obstacle for the transcription machinery.
Friedreich's ataxia is a rare inherited disease, affecting only about 4 in 100,000 people. Often, however, the pathogenic mechanism can be precisely elucidated in the case of rare conditions - as Marc Bühler has now demonstrated for Friedreich's ataxia. This knowledge may then be valuable for other more common diseases. The development of a treatment for Friedreich's ataxia, addressing the problem of incomplete mRNA transcription, would thus not only help to cure a previously incurable disease, but also be useful for other conditions with a similar pathogenic mechanism.

About the FMI

The Friedrich Miescher Institute for Biomedical Research (FMI), based in Basel, Switzerland, is a world-class center for basic research in life sciences. It was founded in 1970 as a joint effort of two Basel-based pharmaceutical companies and is now part of the Novartis Research Foundation. The FMI is devoted to the pursuit of fundamental biomedical research. Areas of expertise are neurobiology, growth control, which includes signaling pathways, and the epigenetics of stem cell development and cell differentiation. The institute counts 320 collaborators. The FMI also offers training in biomedical research to PhD students and postdoctoral fellows from around the world. In addition the FMI is affiliated with the University of Basel. The Director of the FMI since 2004 is Prof. Susan Gasser. This year, the FMI is celebrating its 40th anniversary.


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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.

The life of Marie Schlau, a German Jewish girl born in 1833 hides great unsolved mysteries: accidents, disappearances, enigmas, unknown diagnoses, disturbing murders, love, tenderness, greed, lies, death ... alternatively a different story unfolds every time and takes us closer to the present. Thus, there are two parallel stories unravelling, each in a different age and place, which surprisingly converge in a revelatory chapter.

Paperback and Kindle versions for "The legacy of Marie Schlau" available for sale at Amazon now!

https://www.amazon.com/Legacy-Marie-Schlau-collective-Friedreichs-ebook/dp/B01N28AFWZ

 

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:

https://www.irbbarcelona.org/en/news/international-patient-advocates-partner-to-fund-spanish-gene-therapy-project-to-treat

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:

https://www.irbbarcelona.org/en/news/new-research-front-to-tackle-friedreichs-ataxia
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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