PPMD Research Update: Gene Therapy, Accelerating Clinical Trials & More

Throughout the history of Duchenne, there have been moments that we recognize as inflection points, times when we saw a significant shift in the fight to end Duchenne, when the landscape changed.

The discovery of the gene. The MD-CARE Act. The creation of the Care Considerations. The FDA Draft Guidance for Duchenne. The first approval in Duchenne.

And now, we are seeing systemic gene therapy trials begin to enroll.

All year PPMD has provided you with updates on our Gene Therapy Initiative and the funding we have provided to Nationwide Children’s Hospital ($2.2 million) and UT Southwestern ($255,000) thanks to your generous donations.

There is a tremendous momentum in the realm of gene therapy, and while PPMD always tries to maintain a cautious optimism, it’s hard not to get excited when you see so much progress happening in such a short period of time -- especially for a disease where progress often takes many years or even decades.

And it’s not just gene therapy. Each quarter when we put together these updates, it’s amazing to see so much happening in Duchenne research. Your support continues to allow us to work on attacking Duchenne from every angle.


The Latest Gene Therapy Updates


Drs. Jerry Mendell and Louise Rodino-Klapac will begin to enroll patients for their micro-dystrophin study at Nationwide Children’s Hospital, likely before year end. Supported by PPMD’s Gene Therapy Initiative, Nationwide recently announced that the go ahead was given by the FDA and that it was acceptable to dose the first participant into the AAV-mediated micro-dystrophin gene therapy study. While we didn’t expect any other outcome, it is always reassuring to get the official go ahead from the regulatory agency.

Two other companies, Pfizer and Solid, also have micro-dystrophin gene therapy programs. In fact, Solid recently announced that they will begin enrolling patients for their SGT-001 program. We will continue to provide updates and webinars with companies as information becomes available.


At the same time, the GALGT2 program, led by Drs. Kevin Flanigan and Paul Martin at Nationwide, is also 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 seeks to encourage over-production of a protein that in turn produces other proteins that are important in muscle membrane stabilization and ultimately improves muscle function, as seen in the mdx model.

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.


CRISPR technology, while still a long way off, continues to show incredible promise. Dr. Eric Olson, who PPMD funded with your help as part of our 2016 holiday campaign, presented his results to date at the Wellstone Center meeting in Dallas in September. Read a full recap of this information-packed meeting.

The CRISPR highlight at that meeting was Dr. Olson announcement that he had successfully treated two young spaniels who had Duchenne and their dystrophin was restored. It is encouraging to see results translated from mouse to dog, which more closely represents a human. At this early stage, no firm timelines can be given about when this therapy might get into humans, but these researchers clearly feel the urgency and are working hard to make this happen.

Back in the end of December 2015, three groups all at the same time, announced that CRISPR/Cas9 could be used to improve function of mice with Duchenne. On the heels of that announcement, PPMD moved quickly to fund Dr. Olson and continue the momentum. Now, one of the other researchers, Dr. Charles Gersbach at Duke University is partnering with Sarepta to move the technology forward. While we have yet to learn the exact differences between what the Olson lab and Gersbach lab are doing, we are grateful to have multiple researchers investigating the potential of CRISPR technology in Duchenne and we look forward to more updates from both.

"CRISPR 2.0"

Other novel methods related to CRISPR, which could have a more long term impact, were recently announced. One of these is termed ABE (adenine base editing) is essentially a more refined version of the cutting that the molecular scissors we are familiar with in “classic” CRISPR. A second is CRISPR editing at the RNA level, resulting in temporary, reversible cuts that might have benefit. It remains to be seen if and how these technologies could eventually be applied to humans, and specifically Duchenne. Additionally, a novel delivery method for CRISPR using gold particles was announced that, although in very early stages could be useful. But what this research does mean is that we continue to learn about the potential of this approach and the potential is immense.


Accelerating the Clinical Trial Process

The DuchenneConnect Registry

As you know, our DuchenneConnect Registry team frequently asks you to update your registry account. Sometimes we ask because researchers have requested specific registry data. An article was recently published in Neuromuscular Disorders using data from DuchenneConnect. Dr. Richard Finkel from Nemours Children's Hospital in Orlando, FL led a team of researchers who found that the age at onset of ambulation (age at first steps) is significantly delayed in boys with Duchenne. They suggest that age at onset of ambulation could be a primary outcome measure in clinical trials involving treatment in early infancy. Make sure that you or your child’s registry profile is updated and if you have not joined the registry, do so today!


We have provided you with regular updates on two consortiums formed around the analysis of data from clinical studies and natural history studies. The purpose of these approaches is to analyze existing data to improve design, execution, and analysis of clinical trials. Simply put  -- to design better, more efficient trials and to see more clearly whether and how an intervention improves how a patient feels and functions.

Lengthy trials with variable results, based on endpoints such as the 6-minute walk test that can limit trial enrollment to ambulant individuals with Duchenne  -- this is today’s reality for clinical trials in this disease. But progress is being made and PPMD is proud of our role in changing the clinical trial process. Learn more about current progress that will one day make clinical trials shorter and better for participants.

There’s Plenty More Happening in Duchenne Research

2017 World Muscle Society

The World Muscle Society meeting is the annual gathering that brings together the world’s top neuromuscular clinicians, academics, research scientists, and industry leaders from across the globe. Topics presented here feature breakthroughs and highlights in diseases across the neuromuscular spectrum. PPMD is sharing highlights from Duchenne presentations and posters, as well as the announcements that are being released from companies in our Duchenne space in conjunction with the meeting. Read updates from this year’s meeting, including industry reports.

Robotic Technology

NJIT and Talem Technologies, another project funded by PPMD with the help of your generous support, continue to recruit for the study to explore robotics to assist people living with Duchenne. The team is utilizing NJIT’s technology (an embedded computer, software, a force sensor and motor- add on technology) in combination with the passive, spring-loaded assistance device, developed by Blake Mathie and Talem Technologies.

Other Drug Program Updates

  • Catabasis Pharmaceuticals recently joined PPMD for a webinar to provide a community update on the results from the open-label extension of the MoveDMD trial following 24 and 36 weeks of edasalonexent treatment in boys with Duchenne muscular dystrophy. If you missed it, you can now watch the recording of our webinar with Dr. Joanne Donovan, Chief Medical Officer of Catabasis.

  • FibroGen joined PPMD for a webinar to provide a community update on the development of Pamrevlumab and their FGCL-3019-079 non-ambulatory study in Duchenne, currently enrolling. If you missed it, you can now watch the recording of our webinar with the FibroGen team. To better understand the role of fibrosis in Duchenne, click here to learn more.

  • PTC Therapeutics received a Complete Response Letter from the FDA. In response, the company has filed a dispute resolution, which is a legal process at the agency and includes a full evaluation and review of available data. This process typically concludes within 30 days with a final decision. PPMD continues to work with families to provide the FDA a collective statement around meaningful benefits of ataluren.

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