Little's Life

Little's Life

Saturday, April 28, 2012

Building a Bridge (part 2)

I've learned more about exon skipping and which one will be right for Little.  Turns out skipping 45 is NOT the way to go after all.  Why it didn't occur to me that it would be pointless to skip an exon that was already deleted is beyond me.  I had the right idea with my sweet sweet drawings, by building a bridge over the missing chunk, but I need to elongate that bridge a little.  I was pointed to a website by another DMD mom, Stacy, that gave me a better understanding of how the exons communicate and how to know which ones to target with the drug therapy.  Thank you, Stacy!  I took that knowledge with me to the meeting with Mr. Mendell at NCH last week and talked with him further and he confirmed that I have the right grasp on it.

So here are some new (boring) diagrams, courtesy of (and by that, I mean plagiarized from) the Prosensa website.

This first one is a mock up of all of the exons that carry dystrophin through the body.   The exons have been given shapes as a way of illustrating which exons communicate with which other exons.  Check out the way the shapes are angled.  Like a jigsaw puzzle, only the pieces that match into each other fit together.  Get it?  Check out #s 1,2,&3 - see how 1 fits into 2 and 2 fits into 3?  Well info can flow from 1 to 2, then 2 to 3.  Check out #s 17 & 18.  See how they match end to end?  That's how the communication of dystrophin information flows all the way from 1 to 79 in you and me (people without DMD)

When one of those pieces is missing and the 2 exons on either side of the hole don't match up, you get a boy like Little.  This picture is Prosensa's version of the train falling through the hole in the track.  Mine had a little screaming stick figure in the front of the train as it plummeted into the darkness....this one is just more blocks. pbbbbbbbbbbbt

See how with exon 45 gone, 44 and 46 can't communicate?  This is called an out of frame deletion on exon 45, the clinical term for Andrew's specific mutation.

Now, check out the shapes of the exons nearby.  What needs to happen now, is for that bridge to be built from one over to the next one with matching parts.  Look at the end of  43.  It matches exactly to 46.  So if we skip exon 44, we can connect 43 to 46 with our little drug bridge.

This is actually fantastic news, bc PRO44 trials have been going on in the UK for a while now and they are already in phase 1 here through Prosensa.  So - just as exciting as when I thought PRO45 was the one we wanted!
And what else is exciting about this?  Check out Little's deletion chart again.  We already saw that 43 and 46 can match up, but look at 44 and 47.  Another match!  So skipping exon 46 and building our bridge from 44 to 47 could also be an option one day!

We're still very much in a good place with waiting on these drugs to become available and I'm still incredibly excited about the new exons that are in the Prosensa/GSK line up.  Bit by bit, God is letting these scientists chip away at Duchenne.  I believe that one day our boys will be living with, not dying from a diagnosis of Duchenne.  One day, a mother will get that phone call from her son's geneticist and he won't be giving her the news with tears streaming down his face and sobs choking his voice.  He'll be able to tell her with a reassuring tone that her son will get better.

This will be it for a week or so, I've got some stuff on my plate that will prevent me from blogging (like my borther's wedding!!!!!!!!!!!!!!!!!!!!!!!!).  But as always, thank you for keeping up with us and we'll be back before you know it.  You can still catch be at in the mean time.

And now it's time for our Little's Leaguer of the week, my 50th subscribed reader, Dannadannadanndannadannadanna ooops, sorry Lady, seem to have gotten a little Hicks stuck on my keyboard.
Danna Gentry!
You have no idea how hard it was not to use a picture of you in your sweet 6th grade side pony tail.


  1. I love it! And thanks for not using the 6th grade pic. ;)

  2. my son max is in AVI's trial in ohio for skipping exon 51...its a great drug, have hope for your little guy! _jenn mcnary

  3. That's great to hear, Jenn! I hope Max is really benefiting from it!