Dr. Testi: We find extramitochondrial frataxin in a few unexpected and interesting subcellular locations. We are clearly still working on this as we believe this can be exploited therapeutically.

BabelFAmily: We read that you are working on new set of compounds that are acting on the ubiquitin- proteasome system of frataxin degradation. Can you provide us with an update of this work? Are you working with a pharmaceutical company on this set of compounds?

Dr. Testi: We are now developing small molecule inhibitors of frataxin ubiquitination that appear more effective than those we previously described, at least in vitro. Our goal is to test the more promising leads in the GAA-frataxin animal model of the disease, as soon as appropriate. We are not collaborating with any pharmaceutical company at the moment, but we might in the future.

BabelFAmily: As we have understood from published articles, the discovery that Interferon Gamma upregulates frataxin levels came as a surprise. Can you explain how your newer research focused on Interferon Gamma upregulation of frataxin differs from your past research around small molecule therapeutics? Can you tell us more about  this work?

Dr. Testi: The development of small molecule inhibitors of frataxin ubiquitination is aimed at designing pharmaceutical compounds that act by blocking the physiologic ubiquitination of the frataxin precursor, thus preventing its targeting to and degradation by the proteasome. This should allow more precursor to enter the mitochondria and be processed to mature frataxin. The interferon gamma work originated instead by our independent observation that cells derived from FA patients fail to express an interferon gamma-inducible component of the immunoproteasome. We found that exposure to interferon gamma was able to re-induce the expression of this protein in FA cells, but unexpectedly it also upregulated frataxin. We then confirmed that interferon gamma was capable to induce frataxin in primary cells derived from FA patients. The subsequent collaboration with the group led by Dr. Mark Pook, Brunel University, Uxbridge UK, was instrumental to demonstrate, in the GAA-frataxin animal model of the disease, that treatment with interferon gamma is sufficient to upregulate frataxin in frataxin-defective dorsal root ganglia neurons and to ameliorate sensorimotor performances of ill mice.

BabelFAmily: What are your next steps in Interferon Gamma research? Are there any clinical trials planned? Are there any pharmaceutical companies interested in this research?

Dr. Testi: We are planning to start a pilot Phase II clinical in the fall of 2012. This trial is aimed at verifying whether the subcutaneous injection of interferon gamma is safe and well tolerated by FA patients and whether it is capable of inducing frataxin upregulation. The clinical trial will enroll a small cohort of FA patients which will receive a three months treatment. We are not collaborating with any pharmaceutical company at the moment, but we might in the future.

BabelFAmily: Can you explain more about your FAST project? What are the new therapeutic targets this project will research? Is this project connected with your work on ubiquitin-proteasome degradation of frataxin, or with Interferon Gamma?

Dr. Testi: The Friedreich Ataxia Seeks Therapy (FAST) project funded by the European Research Council is exclusively focused on the development of inhibitors of frataxin ubiquitination, targeting either frataxin or the frataxin E3 ubiquitin ligase, and on their pre-clinical testing in the GAA-frataxin animal model.

BabelFAmily: From your perspective, how far are we from a first high-impact therapy for FA?

Dr. Testi: There is a growing number of highly promising therapeutic approaches to FA currently being tested. As far as interferon gamma is concerned, a success of the pilot clinical trial will clearly encourage the launch of large controlled clinical trials in 2013 aimed at verifying therapeutic efficacy in FA patients. Due to the clinical complexity of the disease, however, it is hard to predict if and when such trials may deliver positive or even conclusive results. Of course we hope they will.

BabelFAmily: Thank you for taking the time for an interview on behalf of BabelFAmily and all FA patients and families around the world. We thank you for your ongoing work towards finding treatments and a cure.

Dr. Testi: Thank you for your interest and support to our work.

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.

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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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