As Sarepta (formely AVI) announces promising results from its phase II interim data and GSK follows up its promising phase II data with a phase III study, things are looking good for an exon-skipping based therapy for Duchenne…if you happen to be in the 13% of those with Duchenne who have a mutation that can be improved by skipping exon 51. For quick reference, this group includes out-of-frame deletions in exons 45-50, 47-50, 48-50, 49-50, 50, and 52.
But for the other 77% of families out there dealing with other types of mutations including other deletions, duplications or point mutations, what does an exon 51 success mean? From the big picture standpoint a success with a drug focused on exon 51 means that we will have, for the first time, a “proof of principle” that the course of the disease can be modified beyond the effect gained by steroids. It means that work on skipping additional exons to include a broader range of mutations will speed up dramatically. It also means that companies working on other types of therapy that are not mutation-specific and their investors will gain confidence from knowing that the disease is not intractable. It means that there will have been established a “regulatory path” or roadmap that can be used by other companies to approve additional drugs. It means that new born screening will become ethically acceptable and we will identify all affected children earlier, which will in turn allow those children to participate in trials of new drugs at even earlier ages.
Not feeling altruistic? Keep in mind that:
Not fast enough? The good news is that it looks like there may be a number of existing approved drugs that may be useful in slowing the progress of Duchenne.
Parent Project Muscular Dystrophy’s mission is to support all those affected by the lack of dystrophin—boys and girls, Duchenne-like symptoms and Becker-like symptoms. We will continue to fund a wide portfolio of research projects that includes both mutation-specific and non-mutation-specific approaches. And we will support the back-up approaches to those approaches. This strategy dovetails with our research plan characterized by the phrase “Better, Faster, Now!” We will put better drugs into clinical testing, we will improve the speed of clinical testing and we will test approved drugs in parallel now. And we will still be in this business until meaningful treatments are available for all of those with Duchenne.
Blog by Sharon Hesterlee, Ph.D.
Read more PPMD Staff Blogs
Comment
Hi David: We are supported both Jill Rafael-Fortney's work at Ohio State University on some of the preliminary mouse work (http://www.parentprojectmd.org/site/PageServer?pagename=Advance_fun...) and we made a grant a few months ago of about $80,000 to Dr. Kan Hor at Cincinnati for the eplerenone study--Dr. Hor is collaborating with Dr. Ramen at Ohio State on this multi-site trial. The Hor-Ramen study isn't yet listed on our Web site because we haven't updated it yet. We have a large batch of grants that we are just about to announce and thought we would do the Web update all at once. But we are definitely funding both the preclinical work and the clinical trial.
Specifically, I'm referring to this study:
http://www.clinicaltrials.gov/ct2/show/NCT01521546?term=cardiomyopa...
Sharon, you wrote: Following impressive improvements in strength in mouse models of muscular dystrophy, a class of cardiac drugs called aldosterone inhibitors (including spironolactone and eplerenone) are in clinical testing now.
And yet I don't see the Ohio State University study through Dr. Raman mentioned in the PPMD portfolio. Will PPMD be supporting this effort? If not, why?
thank you for giving us hope. thank god and ppmd .
ClinicalTrials.gov site says Prosensa's exon 44 skip drug in phase I/II trial will report results this month is this still true.
Hi Amit: Shire's party line is that they are "evaluating" the drug right now and that they remain committed to drug development for Duchenne. I can tell you that the Shire staff have been active in Duchenne meetings and they did have someone at the Connect Conference.
Amit--there was no presentation on ACE-31 at the conference. It's still on hold while the company evaluates the cause of the side effects. Biglycan is moving along--we have just given Tivorsan a $500,000 grant (thanks to everyone who contributed to that!) and MDA has given them $1M. They are working on key issues like dosing and manufacturing and scale-up so that when they go to trial they can really get the details right.
Keith,
Good point, another huge benefit for many under the ACA, the Affordable Care Act is the ability for self employed people to be able to buy decent health insurance when our children have preexisting conditions. For example our family would not be able to get health insurance unless I worked and thankfully as a RN I have been employed by companys that have 50 or more employees so they had to offer group coverage. You are so right every vote counts.
Sharon, was there anything on ace31 in the recent conference?
You did not mention about Biglycan. What is the progress on that?
© 2023 Created by PPMD.
Powered by
Badges | Report an Issue | Privacy Policy | Terms of Service
You need to be a member of PPMD Community to add comments!
Join PPMD Community