There is such exciting news lately about the gains made in treatments for DMD. I attended the conference hosted by Action Duchenne in London a few weeks ago and heard representatives speak from AVI, Biomarin and Prosenza. What I find a little puzzling is why two trials are both testing deletion of exon 51. Is that deletion the most prevanlent form of mutation causing DMD? It seems they are going on next to a trial to treat patients with a deletion of exon 50. How do they make these decisions on which exon deletion to test next? Does anyone have any idea?

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Skipping 51 would help the highest number of patients ~13%. Preclinical work for skipping 50 was paid by Charley's Fund $5 MM (Charley needs 50 skipped): http://www.avibio.com/news_detail.php?newsId=0038
I believe that skipping 51 can also work for a group with deletion of 52 (not all of the 52 group, but some of them)
We found this on the internet. It shows the mutation and what exons would need to be skipped in order to restore the reading frame.

http://www.humgen.nl/lab-aartsma-rus/Table%20point%20mutations.pdf

Not sure if links work in here, we are new to this message board!
Skipping 51 restores the reading frame for a deletion of 52.

http://www.avibio.com/duchenne_muscular_dystrophy.php

Jennifer Shumsky said:
I believe that skipping 51 can also work for a group with deletion of 52 (not all of the 52 group, but some of them)
they are going in the order of the highest population number. the initial test by both prosensa and avi are to make sure that, basically, both technologies work.

after that, the next highest popluated #'s are gonna be covered...which looks to be 50 and 44.

the exons being worked on first are 44 thru 51. my belief is that once the first few are tested and proven affective, the others will move much faster.

i did not read any of the links mentioned above, so if i am am incorrect with my thoughts or if i reiterated anything, plz accept my apologies.
It might be worth noting that, in cases of Becker, mutations involving exon 51 are often noted to be 'particularly mild'. This is also why patch 51 was chosen first. Biggest clinical difference/benefit for the first = more leverage to push for/fund the others.
So, here is my dumb question. Why would AVI agree to a skipping trial involving 50 when there is such a small population of these kids. Is this ethical? Don't get me wrong, i'm all about saving a Duchenne kid but it doesn't seem logical to me. How are they going to find enough kids for this trial? WHy not go for a bigger population of kids as in 51. Doesn't the FDA want to see a good number of kids used in the clinical trials and won't they be measuring the outcome of this trial (i.e., strength testing, ambulation, etc.) as a way of knowing if this drug works? Wouldn't skipping another deletion (i.e., 44 or 45) have a better outcome than skipping 50? So, will the FDA be taking in account the outcome of this trial? I guess what I am saying is, should we be looking at the 'bigger bang for our buck' during these first trials and hope the great outcome from all of this will open the flood gates for all of the other "hot spot' deletion areas and the other remaining exons? Please correct me if I am wrong. I would think we would have to put our first 2 good skips first, that's all.
you're correct, tina. 50 seems to be an exception to the "more bang for the buck" rule of thumb.

i doubt you need an answer to your question for exon 50 though.
This was a pretty shocking information,I guess not every parent may be capable of financing the pharmaceutical industries.I always thought that the Exon skipping should be purely done on the basis of predominant cases.It is unethical if the basic rules is not practiced in finding a cure.Basically if I am wealthy I can let things happen for my son ,if not I can sit behind and just wait for the luck or fate to play a role.Whenever i made donation I never asked which kids will it benefit because I always thought every kids deserves a better life and a cure regardless.I am sorry but I need to vent .
The way this is going, for kids like my son who needs exon 11 skipping, this technology may not even apply. I mean any strategy you take, either you have millions to contribute or you happened to be part of most common mutation, it is in my view unfair to limit the most promising technology to only one or 2 forms of mutations. Every kids deserves a chance at this promise and I think the recent data is showing enough proof of concept that it is time to consider allowing any possible skippable mutations.

Would it not make a better case to FDA if they conduct clinical trials enrolling any skippable patient and providing the proof of benefits?

We certainly donate funds hoping that they(charitable organizations) invest the money fairly and with no bias. Looks like it is time to review whats really going and be smart about our contributions.
In fairness to Charley's fund, they do invest in other potential treatments for Duchenne kids.
My concern is that I would imagine the FDA would want to see the best outcome from this drug after the first trial here in the states. So, you would want to put your best first one and/or first 2 foward. Dr. Ed Connor at CNMC has this exon skipping theory, "leave no Duchenne kid behind." Meaning, we have got to get this right the first time so hopefully the rest will come later at a quicker pace and perhaps even altogether so parents don't have to worry over if they are carrying the 'Golden Willie Wonka' exon skipping ticket or not.
All very interesting thoughts. I agree that is seems unfair and at times even unethical but money DOES make the world go round. I never used to believe that but I sure do now. Money can even sometimes buy health. The drug companies really only have one aim and that is to make money. Is there really anything wrong with that though? It is the political system in which we live - if we want drug companies to all make the same money wouldn't we have to change our entire capitalist system. Communism perhaps? I don't believe that the individuals working in the labs think only about money - I am sure when they treated that Duchenne dog and brought it from almost not walking at all to running down a hallway they must have rejoiced for reasons far deeper than money. But the shareholders of the company are in it for one reason and one reason only - to make money. In defence of Charley's Fund - if you were the parents of a boy who was fortunate enough to win a lottery of 100 million dollars, would you not be tempted to approach a drug company who had already shown success in exon skipping and offer to fund the next trial IF they test the exon your son happens to have deleted? Of course you would. I agree that Charley's Fund did not "win a lottery" and in fact have used monies raised from the public in order to fund the next trial however that is a whole other discussion. It is up to the families of Duchenne patients to become knowledgeable about the various charities and to work to raise funds for the charity that seems to do the most for all Duchenne families. Or - invest in the one that is going to give money to a company that is testing YOUR son's exon deletion next. Ultimately, it is a personal decision. It is a bit of a philosophical discussion - something that has happened over and over again since we found out about our son's diagnosis. This disease is not just a physical/emotional thing, it brings about very deep questions about many different topics.
On a lighter note, the successful skipping of any exon will only open the gates to chemistries that can skip other exons - and from what it seems the drug companies are in discussion with the FDA as well as the governing body in Europe (forget what they are called) to expediate the testing process once exon skipping of one exon has proven to build dystrophin in the cells of the body.
We can't forget that some boys have the disease due to a nonsense mutation or exon duplication - so the 'Golden Willie Wonka (great way of putting it by the way) exon skipping ticket' is useless to them regardless of what company is skipping which exon. Every family needs to count. Every boy needs to matter. Unfortunately we live in a world where sometimes (many times) money over-rules that.

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