This is a blog within a blog. I realize the blog should be my own words, but then again, I found Jill's words say exactly what I think. I just attended the exon skipping meeting at Banberry Center. I think we all agree that exon skipping is a promising strategy for DMD, but it isn't simple and it isn't tomorrow. Prosensa is moving forward. They are involved in a dose escalation study in 3 sites and will analyze the data. The next step is expanded sites (to include the US), this time looking at functional endpoints. In discussion with Gerard Platenburg, he suggested that PTC has set the stage in the PTC124 with outcome measures. While he did not think the 6 min. walk a perfect measure, he believes that this outcome will be used in DMD clinical trials going forward. This next trial will involve a significant number of boys, skipping exon 51. Prosensa plans to roll out other exons (53, 44, 46, 50), but need to get proof of concept with this current trial. They will be biopsying the boys participating in the dose escalation trial and hopefully seeing dystrophin expressed and in sufficient quantity to go forward. What is unknown at the moment is biodistribution. Of course in the mdx mouse, dystrophin was expressed in all muscles. Boys are totally different and there are issues related to turnover and fibrosis that may limit the amount of dystrophin expressed in any one muscle. In boys, one single muscle is biopsied.

AVI biopharma is working currently with the UK group. Dr. Muntoni's group (Hammersmith) has completed the single muscle trial and this week will initiate systemic trials (iv) dose escalation. This is the same road Prosensa is taking. Prosensa is just a bit ahead at the moment. And while this is exciting and first steps are being taken, they are first steps and we all need to understand there has been considerable progress, but progress takes time.

When Chris and Patrick were here, I often felt like I was holding my breath... waiting for that day when Duchenne had treatment and I did not have to worry or rather could have some sort of assurance that everything would be all right. I see the same things happening today, but this time it is attached to a strategy... Parents suggesting to me " when exon skipping works or utrophin is upregulated, life will begin". Like you, I am a believer. I see Duchenne changing and our sons' walking longer, living longer, watching them become adults. I also see promising clinical trials on the horizon. But I do find myself wondering you find yourself holding your breath like I did so long ago, waiting for that perfect day when you don't have to think about Duchenne, when it does not factor into your life. I am hopeful that this will happen 'soon', but I have never liked the word 'soon' because it is impossible to quantify especially when your heart and mind are saying soon is today, next week or next month.

I do know it is about the journey, about living each day, about enjoying your family (*and this family) and finding joy.

From the Caring Bridge site -
WHY I RUN

This is Anthony with Frank Shorter, the gold medalist in the 1972 Olympics for the marathon. We have met him several times and saw him again at the kick-off for the PF Chang's race.

I started running shortly after Anthony's diagnosis in lieu of the wine and prozac which was no longer numbing the pain or squelching the anxiety attacks. I ran for sanity. I ran for strength. I ran away - at least for a little while. When I started, I couldn't even run three miles and within less than a year I did the full marathon in Los Angeles. This year is my 6th race.

Running long distances has taught me how to cope with DMD. For me, the race seems to be the same as our journey with Duchenne. It's all about going the distance. I notice while I train and add miles I never thought possible, there are good days and some not so good days. There are days when I feel I can run forever and other days my legs are lead and my lungs on fire. It takes all I have to just keep trudging along. And there are even the days, I simply can't go anymore and I need to rest. Those days I regroup, let it pass and before I know it, the energy is coming back.

As we listened to Frank Shorter, he made the same parallel about the actual race. Someone asked about the dreaded "wall" and he smiled and explained that when those times come you just hang in there and keep going and it eventually passes. It's just about holding on until things shift back again. His message was about being okay with being uncomfortable and letting it pass...knowing it's going to pass.

These last few months have been so strange for me personally in regards to Anthony on the drug. Everyone reminds me how happy and elated I should be. And I am. But I'm starting to realize now that we are here, there's more to it.

It's true, Anthony is doing great, and let's face it, even if this drug just makes him just STAY where he is and not decline anymore- it's a downright miracle...... him feeling stronger is just icing on the cake.

I thought when we finally got the drug back I would feel as though we reached some proverbial finish line. That we were done and could now be happy. But now I understand...it's just the begnning of another phase. And suddenly, I realize there is no "one day" where we can finally relax and can then begin being happy...where everything is suddenly all perfect. Things will always be precarious becasue that is life and if it's not DMD, it may be something else. It's a marathon.

So now I'm trying to learn it is about staying the course and pacing myself for the long haul no matter where that road leads. I want to continue to learn to enjoy when things are easy and hang in there when it's tough. But I want to stop waiting for that one perfect day when I can feel safe enough to embrace joy for what if I'm chasing an illusion? Instead I want to learn how to ferret out the joy every single day we have now. I want to enjoy the whole run as I add those miles. And I'm sure as always, when I'm in doubt, I can just look at my boys and they will show me the way.

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Staff
Comment by Pat Furlong on October 28, 2008 at 2:28pm
Hello Mirella, You are right, there are plans to skip the above exons. The exact sequence is unknown and will depend on a number of things to include tox studies and efficiency of the dystrophin protein expressed. First off, they have to achieve proof of concept with the first trials. Keep in mind both Prosensa (2-0methyl chemistry) and AVI (morphlino chemistry) are moving forward with systemic delivery exon 51.
Comment by Mirella Kovacevic on October 27, 2008 at 4:58am
Günter Scheuerbrand wrote in his interview with Gerald Platenburg from Prosensa that they have an initial list to skip the following exons: 43, 45, 46, 50, 52 und 53. Is this information right? I hope, because my son has a deletion of exon 53-55.

Staff
Comment by Pat Furlong on October 21, 2008 at 2:43pm
Prosensa and AVI have both mentioned exons 51, 53, 44, 46, 50. There have been mentions of 45, though I think all are concentrating on 51 at the moment in an effort to get proof of concept. Once they have proof of concept (hopefully within the next 12-18 mo.) they are hoping to rapidly expand.
Comment by R Patel on October 21, 2008 at 4:02am
did Prosensa mention anything about skipping exon 43 or 45? or are they only rolling out 53, 44, 46, 50
My son has a delation of exon 44

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