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Trancription by Silvana Mellino Proof-reading by Claudia Guiraldes Subtitles by Krešimir Babić
In her case, she says, Ok, I'll take the fibroblasts (the skin cell).
I will induce pluripotent stem cells from that.
And then instead of nurturing or deriving a neuron
or a cardiomyocyte a nerve cell or a heart cell, from it with FA,
I will do gene therapy on the stem cells.
And then I'll grow cardiac tissue.
I'll grow heart tissue from this cured FA, former FA patient's heart
and I can use that for transplantation into the same patient
who would have a much better chance to retain that tissue
without rejecting it because it comes from their own cells.
So, that you could see it's a very forward leaning, very aggressive project.
But we decided it was time to take that step
and support someone who would take stem cell, cell models into a therapeutic approach.
And it will be very difficult.
It's going to take time, but that, what we are doing now is getting our gene therapy experts.
We will start getting them together with the stem cell experts
and see if our gene therapy experts can help them figure out
how to do the gene therapy on the stem cells before they grow the tissue.
GP: But, may I ask you a question. Is it true that IPS Stem cells lives are not long lasting?
GP: I mean, they can survive a short time?
RB: I know of no serious issue
GP: Yes. Apparently, they die soon, at least.
RB: We have not. I don't know. I have not heard of scientists express a concern that
For example, we are already working together with all the foundations around the world
to develop a program whereby we have a bank for this IPS derived cell models.
So, you know, in this bank they will continue to grow them
and maintain them and distribute them.
So, I know of no serious concern that this would be an issue over time.
Maybe it has to do with the IPS cell before it's nurtured into a neuron.
Maybe you don't have much time. Maybe, you have to handle it very effectively.
GP: Depending on the phase of this?
RB: Yes, maybe depending on the phase. Yes.
GP: Ok.
RB: Yes. It could be that you have to move quickly and well
ML: It could be that it can be still improved
RB: Yes, that's right.
RB: Yes, that's right and I've already said more than I know.
GP: Or maybe it doesn't last long before being differentiated, you know?
RB: That's right. After differentiation, then survives… Right!
GP: So we have to finish also our interview. So what do you think that we can say to our, viewers?
RB: Well, look. Can I go over just a couple of other things?
GP: Yes, sure… Why not!
RB: So Let me go now to just a series of new approaches that we've begun to take.
One is in the iron-sulfur cluster assembly.
We know that the frataxin protein's importance in myocardial function is that
it presents iron in the proper state to iron-sulfur cluster assembly proteins,
so that it's actually the iron-sulfur clusters that move into the mitochondrial membrane
and help transport electrons and so forth.
And they are in short supply in our patients because of the absence, of the shortage of frataxin protein.
So we have one scientist at the NIH, whose project we're supporting,
and it's to synthesize iron-sulfur cluster proteins rather than trying to synthesize frataxin protein
and introduce it so that it does its function in forming these clusters.
She said, "why not try to synthesize directly the iron-sulfur clusters and get them into the mitochondria?"
And it's in early stages we don't know how effective it will be, but we thought it's worth a try.
ML: Who is this scientist working on this issue?
RB: It's Tracey Rouault at the NIH.
And she is widely recognized iron expert
and she's been at our international scientific conferences and chaired some of our sessions.
So…She is a recognized expert in the field.
We are working with Doctor Sid Hecht at Arizona State University on Additional Mitochondrial Agents.
He would like to develop the next generation and then the next generation
of mitochondrial agents like Idebenone, A0001, and EPI 743.
He is working in a very sophisticated way
to see if there are new generations of those molecules
that might even be more effective.
We are also now working with what is called SNP analysis.
SNPs (Single Nucleotide Polymorphism analysis)
In a nutshell, this is a way, of trying to determine why it is that some of our patients
with roughly the same repeat lengths have entirely different forms of the disease.
RB: This Single Nucleotide Polymorphism analysis is
a way we think we can help determine why it is
that some of our patients with entirely different phenotypes, entirely different manifestations of the disease
have roughly the same repeat lengths.
I mean, our assumption has been for some time
that is the repeat length of the shorter allele that determines things like age of onset,
rapidity of progression, severity and final outcome and so forth.
But then you look sometimes in the same families, sometimes in different families,
you see patients with roughly the same repeat lengths
with entirely different ages of onset and severity of outcome and so forth.
So, why is that?
Well, one explanation might be that they have small mutations,
single nucleotide mutations on other genes that somehow affect the FA phenotype.
One thing we are looking at right now, for example, is that may be the gene that's involved in an enzyme,
producing an enzyme that interferes with HDAC inhibition
or interferes with HDAC's work on the protein to silence it.
If we could increase the expression of the gene that naturally is involved in keeping that HDAC away
or if we can down regulate the gene that expresses that HDAC enzyme that silences our gene
and maybe, in this, if we look at enough patients that have such mutations,
and then we see correlate that mutation with their phenotype,
let’s we say we find... we can do two things: we can find a SNP, a Single Nucleotide Polymorphism, in a patient,
in a set of patients and they all have the same SNP on a different gene and they have a milder form of FA,
well, let's work with that as a therapeutic approach;
or we can find one where all the patients that share the SNP
have a more severe form of Friedreich’s Ataxia
we'd want to find a way of suppressing that or changing it.
In either case you have the potential of having a new therapeutic pathway.