Hi All:
I just had a meeting with the famous Dr. Eric Hoffman and what an incredible man he is. I asked him if we should have a muscle biopsy done on our son to either confirm Duchenne or Becker. According to Hoffman, if our son does have Duchenne and not producing any dystrophin, he will be a perfect candidate for exon 51 skipping. If he is producing dystrophin, then he's got Becker. Either way, this is hope like never before.
We have been very hesitant to get the muscle biopsy until Dr. Hoffman said that we only need to have the NEEDLE muscle biopsy done. No need to pur our son out completely - just a local here and it should be quick and more painless. SO much better than putting your child to sleep (dangers of that as well), cutting a large slit and taking out a big chunk of muscle. Dr. Hoffman things that is unnecessary. So, if there is anyone out there who actually had a needle biopsy performed on their child - can ypu please tell me about it and how it went? I have heard folks say that there is no reason to get a biopsy done until a trial comes down and asks for it, but why not have all your ducks in a row - and the exon 51 skipping in atop the lists and we want to be prepared - even if we have to go to London to get on the trials. Thanks for listening.

Views: 172

Reply to This

Replies to This Discussion

From what we've seen so far, the blood work required to do the genetic testing version of diagnosis was able to pick up the deletions. So we did not proceed with the biopsy. Some of my reviews of studies seem to indicate that some will ask for it if it is part of the trial qualifications, otherwise the blood work was sufficient. On the other hand, if the stick is almost the same, why not go ahead. By the way, I found bubbles to be a fantastic distraction with our son.
Hi Noreen,

Was he talking about a skin biopsy? I did not hear about the muscle biopsy done using a needle...it would be great if possible. The skin biopsy is done using a needle and they can see if there is any exon skipping naturally done. I don't think they can see the dystrophin levels though.

Ofelia
What Dr. Hoffman told my husband and myself was to NOT get the full blown muscle biopsy, but to get a needle muscle biopsy. It takes a small portion of the muscle out which is more than enough to detect dystrophin. He likened it to a breast biopsy. They numb the area and then in goes the thin needle - into the leg in this case. I was putting off the regular biopsy due to the invasive nature - wait until a specific trial asks for it. That was until I heard this news. We have an appointment with our son's regular doc, Dr. Robert Leshner at Children's in DC in early October and we will proceed with the needle biopsy from there. Of course we want to know if our son has Becker or Duchenne and we want all the ducks straight prior to exon skipping clinical trials. There is just so much on the verge here, we all have to hope.
I hope this helps - even if just a little.
Thank you! That needle muscle biopsy sounds good. A lot less invasive than the regular one.

Do you know if Dr. Hoffman is working on exon skipping using the PPMOs, the new morpholinos with peptide attached? Is he planning a trial skipping exon 51?

irishgirl said:
What Dr. Hoffman told my husband and myself was to NOT get the full blown muscle biopsy, but to get a needle muscle biopsy. It takes a small portion of the muscle out which is more than enough to detect dystrophin. He likened it to a breast biopsy. They numb the area and then in goes the thin needle - into the leg in this case. I was putting off the regular biopsy due to the invasive nature - wait until a specific trial asks for it. That was until I heard this news. We have an appointment with our son's regular doc, Dr. Robert Leshner at Children's in DC in early October and we will proceed with the needle biopsy from there. Of course we want to know if our son has Becker or Duchenne and we want all the ducks straight prior to exon skipping clinical trials. There is just so much on the verge here, we all have to hope.
I hope this helps - even if just a little.
Yes, this needle biospy is indeed a good thing. And yes, Hoffnman is working on skipping 51 - he said that the doses currently in use will not do much as they are so low. He is working on reducing the toxicity that comes from higher doses. He says look for the trials within the next two years, probably sooner. He is going about this the right way, we feel. Unlike in Holland - where the doses is too low and the drug is old. I will keep you up to date when I find out anything.

Ofelia Marin said:
Thank you! That needle muscle biopsy sounds good. A lot less invasive than the regular one.

Do you know if Dr. Hoffman is working on exon skipping using the PPMOs, the new morpholinos with peptide attached? Is he planning a trial skipping exon 51?

irishgirl said:
What Dr. Hoffman told my husband and myself was to NOT get the full blown muscle biopsy, but to get a needle muscle biopsy. It takes a small portion of the muscle out which is more than enough to detect dystrophin. He likened it to a breast biopsy. They numb the area and then in goes the thin needle - into the leg in this case. I was putting off the regular biopsy due to the invasive nature - wait until a specific trial asks for it. That was until I heard this news. We have an appointment with our son's regular doc, Dr. Robert Leshner at Children's in DC in early October and we will proceed with the needle biopsy from there. Of course we want to know if our son has Becker or Duchenne and we want all the ducks straight prior to exon skipping clinical trials. There is just so much on the verge here, we all have to hope.
I hope this helps - even if just a little.
I've not been on this site in a while, but I can update a wee bit on the punch vs regular muscle biopsy. First of all, you will need to have it done if you are contemplating any clinical trial. Both biopsies require sedation. The worst part is the anesthesia and as long as everyone has a clear understanding that inhalants should NEVER be used, your child should have no problems. The BX (biopsy) is very very simple and generally there are no after effects other than a bit of pain at the site which one gives Tylenol for.
We were told for more than 8 months that we did not need to put our son through the ordeal of a bx - and I still cannot figure out why to this date. My son is 9.5 and runs, swims, rides horses and doesn't conk out until 10:30 pm. I kept on telling his doctor that this is a more a-typical child. Liam is missing exons 48, 49 and 50 - so the trials of exon skipping 51 are right up his alley. But you need to have the bx in order to even be considered for these trials. If it turns out that our son has Becker - ho trials for him, but we rejoyce in the fact that it's Becker. Liam's bx is scheduled for April 10th at Children's in DC. One thing I can tell you is to be extremely on top of things. Educate yourself as much as you possibly can. You can easily learn all your doctor knows and more. We have had to push our doctor for 9 months and live with his hurry up and wait attitude. Exon skipping trials have jumped ahead to IV method of drug delivery. While the current drug at a dose of 0.9 - injected into muscles - has proven to be amazingly effective, they cannot inject a kid's entire body - hence the IV delivery. They have 16 boys in ENgland who are now testing the efficacy of the IV delivery. BUT, results are not expected to be all that great because the dose is too low. Reps from AVI Bio met with reps from Children's in DC (Leshner - Hoffman and more) Avi fired a few folks and the new hires are ready and eager to get the trials up and running here at Children's. More likely, they will begin here because Children's in DC is already set up for it and Dr. Eric Hoffman is here. He is the most generous and fabulous man who really only has the best interests of the boys at heart. This can and will turn a Duchenne into a Becker and Hoffman pretty much bets his career on it. This has already proven to be the biggest thing in the world of MD and have faith that it will come around to help. I was like many of you here when the news of our son's diagnosis it. It was an earth crushing blow as Liam is our only child. If he has an untimely demise, we need to have no regrets about doing all we could for him - we would never get over that. Even if all our efforts come of that untimely end, I will take stock in knowing I did all I could. I am bothered somewhat my parents who seem to take their children for granted. Even prior to the MD, I never took my son for granted, but now I'm in a very different place. I am so able to fully enjoy life and all my boy has to offer. He is very intelligent, bright, funny, crazy, insane, smart, silly and so much more. Life can be ripped from anyone in a split second without warning. Look at Natasha Richardson. Her husband and children never got a chance to say goodbye. We have our chance to say goodbye by living each day with our wonderful children. Things could be so much worse - so much worse. The wonderful people on this site helped me to realize that and I thank you all for your support.

irishgirl said:
Yes, this needle biospy is indeed a good thing. And yes, Hoffnman is working on skipping 51 - he said that the doses currently in use will not do much as they are so low. He is working on reducing the toxicity that comes from higher doses. He says look for the trials within the next two years, probably sooner. He is going about this the right way, we feel. Unlike in Holland - where the doses is too low and the drug is old. I will keep you up to date when I find out anything.

Ofelia Marin said:
Thank you! That needle muscle biopsy sounds good. A lot less invasive than the regular one.

Do you know if Dr. Hoffman is working on exon skipping using the PPMOs, the new morpholinos with peptide attached? Is he planning a trial skipping exon 51?

irishgirl said:
What Dr. Hoffman told my husband and myself was to NOT get the full blown muscle biopsy, but to get a needle muscle biopsy. It takes a small portion of the muscle out which is more than enough to detect dystrophin. He likened it to a breast biopsy. They numb the area and then in goes the thin needle - into the leg in this case. I was putting off the regular biopsy due to the invasive nature - wait until a specific trial asks for it. That was until I heard this news. We have an appointment with our son's regular doc, Dr. Robert Leshner at Children's in DC in early October and we will proceed with the needle biopsy from there. Of course we want to know if our son has Becker or Duchenne and we want all the ducks straight prior to exon skipping clinical trials. There is just so much on the verge here, we all have to hope.
I hope this helps - even if just a little.
I pray that it is Becker's. Exon 51 is such a hot spot that it could easily be spliced out even if DNA sequencing shows its existence which could explain your son's a-typical progression.
Thanks and I appreciate your words. I have found out further that most hospitals will not do punch or needle biopsies on children under 10 years of age. Furthermore, both types of biopsies require sedation which is the main worry. Our son will undego the regular BX April 10th. His surgeon says the only real worry is the sedation - and as long as you do not allow inhalants, all will be well. Liam should even be able to easily walk out of the out patient center after the procedure. I do have to tell you that our doctor at Children's here is DC gave us the appearance that he has all but given up. He put us off and off again over the bx. He just shook his head as we presented him with an 8 year old boy with a-typical symptoms and he did nothing. Then I got an email from him intended for another doctor by accident and the entire WORLD changed. He is all over our son now and with VERY good reason. I do feel that God works in mysterious ways and thankfully, I got the email intended for another.
We've met Eric Hoffman a number of times and he is the key to helping the boys and those with MD. He really has the kids best interests at heart. We feel very lucky, not only to have gotten this email, but to have Eric Hoffman right here where we are.
Thanks again.

MarcosDad said:
I pray that it is Becker's. Exon 51 is such a hot spot that it could easily be spliced out even if DNA sequencing shows its existence which could explain your son's a-typical progression.
Hey - I forgot to ask if you could please explain further what you mention about the splicing - at more of a 3rd grade level? Haha! Thanks

MarcosDad said:
I pray that it is Becker's. Exon 51 is such a hot spot that it could easily be spliced out even if DNA sequencing shows its existence which could explain your son's a-typical progression.
The surgeon is right - the only concern is the anesthesia. Go over it as many times with his surgeon and the anesthesiologist so you are comfortable with what they will be doing. For my son (who was 5 at the time) they let us be there for the anesthesia delivery. First they had my son drink something that made him woozy, then they injected the anesthesia (which can be a little painful through tiny veins). The biopsy procedure itself is quick; it was over and done with before I had time to worry about it. Your son will be walking home after the procedure, no doubt about it. I hope you get the results you're hoping for.
That makes me feel quite a bit better, thanks! We are very comfortable with the entire deal. We adore the surgeon and the anesthesiologist is a long time friend of my brother, who is also a pediatric anesthesiologist. We just need to have all of our ducks in a row for the upcoming exon 51 skipping trials which will require a bx for baseline. We were put off again and again by our doctor who would NEVER offer any possible reasons for why our son, at 9.5, is running, jumping, racing, swimming, riding horses without tiring at all. At this point, we must know if we are actually dealing with DMD or BMD. DMD will have his ready for the trials and BMD will just be grand. Either way, we feel very good - considering this crummy disease.
I really appreciate the time you took to respond to me - it means a lot. Thanks


CVita said:
The surgeon is right - the only concern is the anesthesia. Go over it as many times with his surgeon and the anesthesiologist so you are comfortable with what they will be doing. For my son (who was 5 at the time) they let us be there for the anesthesia delivery. First they had my son drink something that made him woozy, then they injected the anesthesia (which can be a little painful through tiny veins). The biopsy procedure itself is quick; it was over and done with before I had time to worry about it. Your son will be walking home after the procedure, no doubt about it. I hope you get the results you're hoping for.
There are alot of cases around exon 51 where the DNA sequencing predicts an out of frame mutation, however, the boys are showing atypical progression. So is this a site that exon skipping naturally occurs often or is it more prone to splicing errors and thus 51 itself will get spliced out or possibly a pseudo exon appears before 51. There are exon dependencies on introns that could cause an exon to be spliced out and also there are mutations that extends into the intron from 50 towards 51 that could cause a pseudo exon (a new exon) to appear out of an intron during translation that can put it back in frame. Unfortunately without a cDNA analysis one can only surmise what is going on. The point being 51 tends to be where this happens often and your son may be one of the lucky ones.

So to explain this better. If your son's mutation shows exon 50 as being deleted, it doesn't say how far into the intron this deletion occurs. If this deletion happens to trigger 51 to be spliced out during transcription into mRNA then the reading frame is restored. If there are other mutations occuring in the intron, this could cause it to look like an exon which will be spliced in during transcription (i.e. exon 50 is created now your back in frame again). This seems to be a region where adding an exon or removing an exon puts it back in frame so a mutation that may look bad in a DNA analysis may actually look better in a cDNA analysis (where they analyze the mRNA sequence).

If you are considering doing an open muscle biopsy, make sure you have enough specimen saved to do a cDNA and/or Western Blot test in case the immunostaining doesn't help much (immunostaining is the cheapest method and also not the most precise). I've been down this road. My son show signs of an MD, immunostaining shows DMD characteristics, Full blown DNA test showed no mutations, cDNA showed no mutations, Western Blot test showed normal levels of full weight dystrophin. Did all the other DNA MD tests, spent fortunes and still no dx. Now they want to do another open muscle biopsy and I'm resisting because my son's last biospy keloid.

irishgirl said:
Hey - I forgot to ask if you could please explain further what you mention about the splicing - at more of a 3rd grade level? Haha! Thanks

MarcosDad said:
I pray that it is Becker's. Exon 51 is such a hot spot that it could easily be spliced out even if DNA sequencing shows its existence which could explain your son's a-typical progression.

Reply to Discussion

RSS

Need help using this community site? Visit Ning's Help Page.

Members

Events

© 2021   Created by PPMD.   Powered by

Badges  |  Report an Issue  |  Privacy Policy  |  Terms of Service