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:

  • There are two drugs in the “healthy volunteer” phase of testing that increase the amount of utrophin, a protein that can stand-in for the loss of dystrophin (Summit PLC, Pfizer) and another two that are in the preclinical lead-up phase to a human study in Duchenne (PTC Therapeutics, Tivorsan).
  • There are two drugs in development that may be able to produce the positive effects of prednisone without the side effects, one in testing in healthy volunteers (Catabasis) and one that has been partnered by the National Institutes of Health to move it toward clinical testing (Reveragen).
  • Idebenone, a strong antioxidant, is in phase III clinical testing for Duchenne (Santhera).
  • Nationwide Children’s Research Institute is testing the ability of a gene called follistatin to increase muscle mass in Becker muscular dystrophy via gene therapy.
  • None of these approaches are mutation-dependent.


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.

  • Currently in clinical testing are phosphodiesterase inhibitors Sildenafil (Viagra®) and Tadalafil (Cialis®), which may overcome the reduced blood flow experienced by people with Duchenne when the muscles contract and may do other helpful things that aren’t clearly understood yet.
  • 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.
  • Another study, supported by Charley’s Fund, is evaluating the potential benefits of insulin-like growth factor.


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

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Comment by Jason Darienzo on August 9, 2012 at 7:03pm
Comment by Sharon Hesterlee on August 9, 2012 at 5:50pm

Ofelia--I actually forgot to mention the Pfizer myostatin inhibitor that's in safety testing in healthy volunteers now...the plan is to move to Duchenne if all goes well in this first phase.

Comment by Ofelia Marin on August 9, 2012 at 4:50pm

Wouldn't be great if ACE-031 was back on track? Adding a myostatin inhibitor can posibly help our sons more, they are getting older and losing significant muscles mass by the time the drugs on the list get close to approval. It is quite diffcult to see exon skipping helping slow lower body progression only if the boys start treatment before the 'tipping point'.

Comment by Keith Van Houten on August 9, 2012 at 11:11am

Lots of good stuff in the works.  Doctors and scientists are clearly hard at work to help our boys.

An equally important battle will be fought by politicians in Washington DC over the next year. 

Many of these treatments will be phenomenally expensive.  Insurance coverage will be critical to enable boys to actually have access to any treatments that get approved.

Under health care reform - "Obamacare" - boys cannot be dropped from insurance coverage because they're sick, they cannot be denied coverage because they're sick, they cannot be charged more because they're sick, and they can't run out of coverage because their medical care is too costly.  All of these things can, and did, happen prior to health care reform.  I believe they are even more likely to occur when you're incurring medical expenses of the magnitude we're talking about with something like exon skipping.

Just something to consider.  Your vote matters, and elections have consequences. 

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