Links to the other five scientific presentations from Encuentro Ataxias (Ataxia Encounter) 2008:
First presentation: 
Dr. Manuel Álvarez Dolado, Principe Felipe Research Center, Valencia, Spain:
“Advances in research into regenerative mechanisms for cellular fusion in ataxias”
Second presentation:
Dr. Eulalia Bazán, Research Team, Ramon y Cajal University Hospital, Madrid, Spain: 
“Presentation on the advances in the research project into growth factor LGF, which acts as a possible treatment agent for different types of ataxia”
Third presentation:
Dr. Javier Díaz Nido, Severo Ochoa Molecular Biology Center, Autonomous University of Madrid, Spain:
“Gene Therapy in Friedreich’s Ataxia:  Cellular Models of Olfactory Bulb and Their Repercussions on Patients”
Fourth presentation:
Francesc Garsó, Director of Brudy Technologies, Spain:
“Cellular antioxidant based on DHA:  possible treatment for the deterioration of peripheral vision in several cases of ataxia patients”.
Fifth presentation:
Dr. Salvador Martínez, Alicante Institute of Neurosciences, Miguel Hernandez University, Spain:
“Plans for applying stem cells in spinal ganglia in Friedreich’s ataxia”
°°°°°°°°°°°°°°°°°°°°°°°°°° (ESP)
Summary by Mari Luz Gonzalez Casas
Translation: Tom Sathre
To hear the entire presentation in Spanish on mp3, go to the following link:
Encuentro Ataxias (Ataxia Encounter) 2008
Organized by the
Colectivo Ataxias en Movimiento
(Ataxias on the Move Coalition) 
Madrid, Spain
Madrid, April 29, 2008
Sixth scientific presentation:
Dr. Joaquim Ros of the University of Lleida - Selective oxidative modification of proteins in yeast models of Friedreich’s ataxia
 Dr. Joaquim Ros
Dr. Joaquim Ros and his team are specialists in the biochemisty of oxidative stress using the yeast model.  
Yeast cells have a protein, named YFH1, that is structurally very similar to human frataxin, the protein that is lacking in human Friedreich’s ataxia.  In yeast models that lack this protein, function can be reestablished by introducing human frataxin.  Therefore this justifies using these yeasts as a model to understand mechanisms that underly this pathology.
Yeasts share several aspects with mammals:
1.      Localization of this protein [YFH1] in mitochrondria.
2.      Iron accumulation in the same form in yeasts and in mammals.
3.      Lack of activity, both of enzymes that contain iron-sulphur compounds, and of their iron-binding function.
When the proteins of cells lacking YFH1 (the gene for frataxin) are compared with those of cells that do contain YFH1, it is seen that there is a series of different proteins in cells that lack frataxin.  These proteins were identified using mass spectrometry techniques; it was seen that all of them were related to oxidative stress.
There is a series of proteins related to antioxidant defenses, among which are mitochondrial and cytosolic proteins.  Of all these, the most important are the superoxide dismutases [1], or SOD, which catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. That is, they destroy the reactive oxygen species (ROS), the ones which would give rise to free radicals of oxygen that harm the macromolecule.  
So the superoxide dismutase enzyme is an important antioxidant defense in the majority of cells exposed to oxygen.
Like the other proteins, the dismutases were increased in the cells that lacked frataxin. The activity of these proteins was measured and, surprisingly, despite the presence of more proteins, their activity was nearly non-existent. That is to say, there was an antioxidant protein, expressed in large quantities, but with very little activity.
Two possible causes were considered:
1.      The protein can be changed.
2.      The protein lacks its cofactor.
In this particular case, the cofactor of the SOD is manganese.  Measuring manganese in these cells leads to the conclusion that the concentration of manganese was very low, which perfectly explains why, although the protein was present, there was very scant activity.
Upon substituting the standard level of manganese in the cell, the activity of (the) SOD was fully recovered, and along with it the antioxidant capacity of the cell.
On the other hand, proteins that contain iron-sulphur complexes are proteins that are being damaged, that are losing their activity in this cell model.  Thus, when SOD activity is recovered with manganese, many of the proteins also recover their activity.

[1] Dismutase = generic name for enzymes catalyzing the reaction of two identical molecules to produce two molecules in different states of oxidation (
Your questions answered:
What is the consequence of intracellular iron accumulation?
When superoxide anions accumulate – and this can occur due to the low activity of SOD – they produce an increase in hydrogen peroxide, accompanied by an increase in intracellular iron.  What merits special attention is iron in its ferrous form, because it is capable of giving up an electron and forming hydrogen peroxide, and this in turn, supported by ferrous iron, is able to produce the harmful hydrogen radical (OH). This radical goes on to damage macromolecules, such as proteins, DNA, membrane fluids, etc.
Do cells deficient in manganese also accumulate ferrous iron?
By means of flourescence it was demonstrated that, indeed, there is an accumulation of ferrous iron.
Upon producing the radical OH-, the protein begins to change its structure, and a part of this alteration is the formation of the so-called carbonyl groups.
The formation of this change is limited to specific sites on the protein, and it involves the loss of function of this protein.  The up-side is that these modifications are easy to detect. It is possible to mark this protein with a chemical agent, and once marked, the protein can be detected using basic biochemical techniques.  Thus it was possible to verify that proteins had oxidative damage specifically in the cells that lack the YFH1 gene.  In addition, it was necessary to determine whether these proteins are important for the cell.
Conclusion:  Some of these proteins are very important, since they are, for example, subunits of ATP synthase.  ATP synthase is a mitochondrial protein that gives us energy via synthesis of ATP, and therefore the loss of its function can be very problematic for the cell.
If this experiment of oxidative damage is done with an iron chelator, desferrioxamine, present in the culture medium, then the oxidative damage is much less. Here the experiment is shown with pyruvate kinase, but  any other protein could have been selected.
Dr. Ros’s team has not done this experiment with other chelators such as deferiprone, but the possibility exists of doing that soon.
From this study of proteins we also derive these conclusions:
1.      The majority of these proteins are mitochondrial.  This is not surprising since the accumulation of iron and the lack of frataxin are expressed in the mitochondria.
2.      Many of these are proteins that combine with magnesium directly or through nucleotides.  Keeping in mind that some iron-bonding proteins, the iron-sulphur proteins, can lose iron through the effect of the radical, the superoxide anion,    Included  in this group are proteins that combine with iron-sulphur compounds, and are able to effectively lose it by the radical – the anion superoxide. This provokes an increase of intracelular iron, as well as starting up mechanisms that also are able to make use of iron outside the cell. Because of the augmentation of that intracellular iron the team is able to substitute magnesium in physiological form and functionality. This is combined with specific proteins and by that method is to promote the catalysis of oxidative stress.
Furthermore, triphosphate nucleotides, such as ATP, GTP, etc., have a huge capacity to combine with ferrous iron ions.  Therefore, increasing this quantity of iron could promote the substitution of iron for magnesium through ATP and therefore provoke more oxidative damage to these proteins.
Concluding, all this gives us the key to the reason that oxidative damage specifically affects these proteins and these mechanisms, and nevertheless does not affect all proteins more generally.
We have seen that supplementing these cell cultures with manganese entails a reestablishment of antioxidant capacity.  In the next stage of investigation, manganese and traces of copper were added to the culture medium. (Copper is a cofactor of another isoenzyme of SOD, with which antioxidant capacity is more completety reestablished.)
Dr. Ros and his team have recently begun experiments with cultured nerve cells in order to see if the conclusions set forth in this current work can be validated or not, and for this they are going to use the effects of RNA-interference of the frataxin gene on these neuroblastoma models, using lentivirii. Preliminary results thus far show that already they have detected a certain interference of the frataxin gene and an increase in the quantity of SOD2, as well as a decrease in its activity.
In eukaryotic, higher cells, the influence of manganese levels will also be studied, as well as how those levels affect the enzymes that are involved in very important metabolic processes inside the nerve cells. For example, pyruvate carboxylase, among others, is an enzyme that makes use of manganese. The team will be determining if these enzymes show an activity deficit in these systems.

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!


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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