Expanding PPMD’s Gene Therapy Initiative

This holiday season, PPMD is asking you to support our ongoing Gene Therapy Initiative. Gene therapy has dominated the headlines this year in a number of diseases, including Duchenne. There is such extraordinary potential – and uncertainty – in this technology that we as a community must explore. PPMD is proud of our 23+ year history, investing in innovative therapies and science. Nearly every therapeutic in the Duchenne pipeline has been supported by PPMD. Gene therapy could be the future and we are committed, with your help, to explore this science from every angle.

That’s why, earlier this year PPMD launched our most ambitious effort to date: our Gene Therapy Initiative. The Gene Therapy Initiative is a long-term concept seeking to accelerate the potential of gene therapy as a therapeutic option for Duchenne.

We kicked off this initiative with last year’s holiday campaign and, thanks to your generosity, an investment into Dr. Eric Olson’s CRISPR exploration at UT Southwestern in January. That same month, we provided our largest single grant to date to Dr. Jerry Mendell and Dr. Louise Rodino-Klapac and the team at Nationwide Children’s Hospital to further their exploration of microdystrophin gene transfer.

Our early strategy was to bring attention to and fund critical questions that must be answered in order for the technology to move into human clinical trials. And we are excited to see that, in less than a year of our funding, multiple gene therapies are on the eve of dosing their first patients.

PPMD is raising $400,000 to expand our Gene Therapy Initiative—our biggest holiday goal to date! By supporting the expansion of our Gene Therapy Initiative, you are helping PPMD fill critical gaps in the development of these technologies so that they can maintain their momentum.

Our recent victories are a testament to what we’re capable of when we come together as a community. But as proud as we are of everything we’ve accomplished, we won’t rest until every family can turn to a treatment to end Duchenne.

We believe that the expansion of gene therapy is critical to that fight and we hope you will consider supporting this initiative.


The first project PPMD was able to fund as part of this initiative was an initial exploration into the safety and efficiency of CRISPR/Cas9 genome editing to correct muscle abnormalities associated with Duchenne. PPMD’s grant to the laboratory of Eric Olson at UT Southwestern brought focus to essential questions:

  1. Are there potential off target effects with CRISPR? Given the fact that it is editing the DNA, it is essential to ensure this is safe technology since the gene is being permanently corrected.
  2. How stable and efficient are the proteins produced by CRISPR? Given that there are a number of strategies to deliver a microdystrophin, it is wise to compare the stability and functionality of the proteins produced by CRISPR and other micro dystrophins.

Dr. Olson has examined the potential for off-target effects by sequencing computationally predicted off-target genes. Significant off-target effects have not been seen.  As such, this project is moving onto the next level of the therapeutic development pipeline.

PPMD will remain committed to this partnership throughout the next several years as moving CRISPR into human trials becomes more within reach. This first generation CRISPR will use an AAV delivery system.  We are also in discussion with other labs who are exploring ways to optimize the CRISPR technology as a potential treatment for Duchenne, for example through delivery mechanisms other than AAV. As has been seen in the press recently, CRISPR is a relatively young technology and there remains many improvements to be made. We believe in the potential of CRISPR and want to support its development to create the best therapeutic for every individual with Duchenne.


Luckily there are a number of strategies moving forward into the clinic that will use the AAV delivery system, including PPMD’s largest research investment to date, a milestone driven award to Dr. Jerry Mendell and Dr. Louise Rodino-Klapac of Nationwide Children’s Hospital to explore a microdystrophin gene transfer via AAV rAAVrh74.MCK delivery in Duchenne. This will not only test the potential of using microdystrophin as a dystrophin restoration strategy but also give us a read as to how well AAV delivery in general might work in Duchenne.

This investment is to carry out a Phase 1 clinical trial designed to explore several issues confronting gene therapy such as how well the virus can deliver systemically, and whether an immune response will be induced by the virus or the microdystrophin produced. Knowing these answers will help us maximize our knowledge of safety and efficacy and apply these learnings to all individuals with Duchenne.

Since January, Drs. Mendell and Rodino-Klapac have made great progress, submitting and receiving acceptance of an Investigational New Drug (IND 17763) from the FDA. They have also completed the production of clinical grade virus for the study and hope to dose their first patient(s) before year end.  

This project has moved into the clinic in under 11 months. This fast pace has increased competition and momentum in gene therapy initiatives. Nationwide’s gene therapy approach will inform us (the field) in terms of safety, delivery, integration into muscle and heart, and expression of microdystrophin.

Looking Ahead

As with all of our other investments we believe it is essential to accelerate options for all individuals diagnosed and invest in work across approaches, targets, and methodologies. At this early stage, it is prudent to diversify and invest in other gene therapy strategies in order to develop options for all.

Our sights are set on driving therapies into the clinic, working towards making gene therapy a potential option across the trajectory of Duchenne. This includes following our current investments, working to expand the field, and ensuring that there is a regulatory path forward.

PPMD plans to expand our Gene Therapy Initiative by taking a closer look at Dup2 and examining and potentially investing in additional projects, like GALGT2.


The GALGT2 program, led by Drs. Kevin Flanigan and Paul Martin also at Nationwide, is moving ahead with the announcement that the go-ahead to dose the first patient was received by the FDA. This gene therapy strategy is different than the microdystrophin therapy, as it does not work to replace dystrophin. Instead, it seeks to encourage over-production of a protein that in turn produces other proteins, such as utrophin, that are important in muscle membrane stabilization and leads to  improved muscle function.

This therapy would be appropriate to all individuals with Duchenne and in fact, could be helpful for other muscular dystrophies as well.

Both the micro-dystrophin and GALGT2 programs at Nationwide are licensed commercially by Sarepta Therapeutics. While Sarepta’s involvement is certainly a nod of approval for proof of concept, there still is more research to be done which takes more funding.

It will take the ongoing support of patient advocacy organizations and programs like PPMD’s Gene Therapy Initiative to keep these studies moving forward during this critical stage.

The possibilities of gene therapy in rare diseases like Duchenne continues to expand and evolve at an incredible pace. But we know that nothing comes quickly enough for our loved ones living with Duchenne. That is why, with your support this holiday season, PPMD will continue to explore, evaluate, and invest in the portfolio of gene therapy possibilities that will help every single person in our community.

Thank you for joining the fight to end Duchenne this holiday season by donating to PPMD’s Gene Therapy Initiative.

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