Heart Failure Drugs Preserve Muscle in Muscular Dystrophy

What about this, any comments?

Both of them are apporoved drugs, farmacological approach and near treatment?

Am I missing something or this could be very promissing ...at least?



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Lisinopril is widely used for cardiac issues for mid-range boys with Duchenne, sometimes before cardiac symptoms appear, usually after. My son was prescribed lisinopril pre-symptomatic at age 10, but with it took a lot of pushing, because they have not gotten far enough with the human research proving it helps before symptoms show (in our cardiologists view). The usual starting dose I've heard from other families for kids this age may be small 2.5 MG but most increasing over time to 5MG, pre-symptomatic. After symptoms, I don't know the dosage range. You can make the case that cardiac degeneration is an inevitable symptom and therefore should be treated like it's coming. And if it helps overall muscle, too, so be it. Sneaky but true.
This is the full article about lisinopril+spironolactone in mdx.

Thank you so much Ofelia for sharing that.

If I'm reading this right, from the article the dosage of lisinopril was 10mg/kg/day. For spironolacatone, 37.5mg/kg/day. That is much, much higher dosing than normally prescribed for management of heart failure.

For my son, that would be close to 700mg of lisinopril per day, and 2600mg of spironolactone!


It would be great to hear from PPMD if they support the rather bold statements in the paper that this study demonstrates "preservation of function to an extent that far exceeds that of any prior pharmacological therapy regimen studied in mouse models of DMD."

Juan - it appears PPMD agrees that there is promise here...


Yes David hopefully it will help our sons through until someone cures them definately!!!
I am already using it with no sideeffects yet.

I must say it's a little disappointing to have our questions to PPMD answered in such an indirect fashion.

The research was posted, Juan raised the question in early August, and a few weeks later we see press releases on the same topic. It thought these forums were a way for parents to gain more direct access to PPMD, but it appears that PPMD no longer participates in these forums so I feel we've reverted to monitoring Google alerts, etc.

Hopefully the lack of participation is a sign that they are just too busy with real opportunities for treatment to bother with questions from parents.


I agree that someone from PPMD should follow our discussions, sharon Herstlee did some time ago, still it is great to chat with other parents, I live in Perú and I can´t feel the distamce when it comes to accurate information and positive vibes coming from all people in this mini "facebook"...David thanks for pointing the importance of someone from PPMD checking this forum.

These are great questions! I've forwarded them on to the appropriate PPMD staff member who can provide some insight on this discussion, so check back soon for a response!


David- We do make a point to monitor the community site, but unfortunately can't catch everything. If you ever feel like a discussion has not been adequately addressed, or would like an "expert" to chime in, please do not hesitate to bring it to our attention by sending us a message or email! We would be glad to help.


As always, we hope you find the community site to be a valuable tool that allows families all over the world to connect with each other to chat and share stories, news, and information related to Duchenne. 




No, you aren't missing anything except that we don't know if you need to use both drugs together or if you can get the same effect from just one or the other.  We also need to know if it matters when you start treatment to be able to set up a clinical trial.


PPMD has just funded a quick (six month) follow-one study to answer these questions in preparation for launching a human study.  This is the abstract of the follow-on study we are funding:


Jill Rafael-Fortney, Ph.D., Ohio State University

 158 - PPMD Bridge/Exploratory Funds
 210 - Optimization of renin-angiotensin-aldosterone inhibitors as a treatment for dystrophin-deficient skeletal muscles and heart.
 Bridge Grant


We have recently observed a profound improvement in a mouse model of Duchenne muscular dystrophy resulting from treatment with the FDA approved drugs lisinopril and spironolactone. Muscle strength in skeletal muscles in limbs and those used in respiration was doubled in treated mice compared to untreated mice and function of the heart was also significantly improved. Ongoing muscle damage in skeletal muscles and heart was almost completely prevented. This project aims to define the parameters required for optimal treatment of dystrophic mice. These studies have direct implications for designing clinical trials for the DMD patient population.




Sharon Hesterlee, Ph.D.

PPMD Sr Director of Research



David--just saw your comment about wanting more direct interaction.  I can only say that we have funded such an unprecedented amount of research this year that I have been scrambling for months to keep up.  I hear you though and will make a concerted effort to keep following and reporting to these forums.


Also, you are all welcome to email me directly at any time if you have questions (sharon@parentprojectmd.org).  If it's a question of general interest I'll try to make sure to repost the answer where appropriate on the community site. 


Best Wishes,



Thank you Sharon. Those of us with sons who are unlikely to benefit from exon skips are desperate for some signs of a therapy that will help and will help soon. Utrophin upreg is proceeding at a snails pace. ACE-031 has disappeared from the radar and I can detect no sense of urgency to restart it.

These drugs present hope because they are not mutation-specific and they would presumably have a relatively simple approval process. But questions remain:

Will it move quickly to phase 1? with no particular pharma company to benefit, is it likely that this will spend years in pre-clinical phase and animal studies? If this has little chance of entering phase 1 within 2 years then I will look elsewhere, my boy does not have that kind of time.

Also, do these results suggest that losartan users should consider switching to lisinopril? I realize the dosages being studied here are much higher than what is being prescribed as preventative medicine. My son takes 25mg/day and he is 150lbs. But my cardiologist won't make a recommendation until "losartan vs lisinopril" study completes, which is many years away by his estimate. Does PPMD feel these studies tilt the scales in favor of lisinopril (if replicated) even before the other study completes?

Hi David:


I suspect Shire is trying to tweak ACE-031 so that they won't get the side-effects (nose bleeds)  that occurred in the phase II study.  That takes some time, but I wouldn't say they don't feel urgency about it--they have a bottom line to meet financially and time is money...so whether or not the motives are the same the goals are aligned.  But to be fair, they have said that they are "in this field to stay" and that they want to make a difference.


As for the lisinopril/spironolactone combination--since these drugs are already on the market the costs for getting them approved for a new indication are considerably lower than the requirements for a drug that's never been tried in humans before.  It also can be a faster process.  I should hope that we could start a phase I study in less than a year and that is certainly something that PPMD would either fund or contribute to funding.


At this point I don't think anyone would recommend switching from losartan to lisinopril.  There is actually a study going on now at Nationwide Children's funded by MDA that is comparing those two drugs head-to-head.  It's been going on for a while already so results should be due soon...but Dr. Rafael-Fortney's results suggested the spironolactone may be required to get the really impressive results she saw in skeletal muscle (as well as lisinopril).  That's what we've funded her now to find out in a quick mouse study--can you use either drug separately or do you need both together?  This will lay the foundation for a human clinical study.





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