As you know by now, September is Duchenne Action Month. And while the idea behind this campaign is to encourage our community to take action, the momentum in Duchenne research has never felt more active...and promising.

Highlights from this quarter are included below. Your support continues to allow us to work on tackling Duchenne from every angle. Thank you for your continued belief in PPMD.

Our Gene Transfer Initiative

Progress continues in microdystrophin gene therapy

Research Update

On August 30, the FDA approved Kymriah, a gene therapy that treats an aggressive type of leukemia, for children and young adults. For our Duchenne community, on the brink of starting gene therapy clinical trials, this news is another piece of evidence showing the tremendous strides this technology has made and reinforces PPMD's decision to heavily invest, with your help, in gene therapy through our Gene Transfer Initiative. With our $2.2 million grant to Dr. Jerry Mendell, Dr. Louise Rodino-Klapac (co-PIs), and Nationwide Children’s Hospital in January, the trial at Nationwide is making tremendous strides towards entering the clinic in the last quarter of 2017.

This approval means that there are regulatory and commercial pathways for cell and gene based therapy. It means that you can put living DNA into a human and it can do its job. And it means that years of scientists making seemingly incremental advances can all come together and result into a giant step forward. A step forward that we believe will move this technology in a direction that will eventually benefit our community, our children. PPMD is pleased for the patients that can benefit from Kymriah and optimistic about what gene therapy can do to help end Duchenne.

Gene therapy suffered some setbacks in the late 90s from concern over immune response to the virus (vector). The technology was temporarily slowed as researchers dug into how to get around that issue. Recently the adeno-associated virus has been used in gene therapy programs in other indications, including SMA, with success. One major difference though the SMA example uses an intrathecal (into the spinal canal) delivery and microdystrophin gene therapy will be delivered systemically (IV) by infusion.

The SMA example is not an apples to apples comparison, but the proof of concept is there. Secondly, in SMA the product was delivered to very young infants, with no problems to date. There are reasons to deliver the therapy to young patients:

  • They have a more naïve immune system so theoretically less patients will have been exposed to AAV, which would exclude them from early clinical trials.

  • Less vector needs to be delivered which, from a manufacturing standpoint, allows more patients to be treated.

  • Younger patients have less damage from the disease, so hopefully it will be easier for a treatment to have a sizable effect.

We are hopeful that the same success will be seen in Duchenne. It seems a good place to start and with success, we anticipate the field will rapidly expand protocols and seek approvals. Fingers crossed!!

Long term success seen in dogs

News Update

As was reported in Nature recently, long term success has been seen in dogs receiving gene therapy. While a dog is not a human, this bodes well for positive results in humans. And the Kymriah approval also shows that a one-time dose can have a substantial, lasting effect. In earlier gene therapy research, persistence of treatment was a question, and with these recent examples, that question is being answered. This, combined with the ability to package a shortened but functional microdystrophin into the capsid (virus shell), has been instrumental in moving the field forward.

PPMD continues educational webinar series

Research Update

Clearly, the field is optimistic as there are three different programs (Nationwide Children's Hospital, Pfizer/Bamboo, and Solid Bio) delivering a shortened but functional copy of the dystrophin gene via an adeno-associated virus, expected to begin within the year, with the Nationwide Children's Hospital program to start sometime in the last quarter of 2017.

PPMD’s August webinar on gene therapy provides a lot of background information on the technology itself, including some of the nuanced differences between the microdystrophin genes being delivered by the three programs, and other ways the programs vary.

Microdystrophin gene therapy would eventually be available to all individuals with Duchenne. For some of the early trials, patients with high levels of antibody to the AAV or with mutations that have the highest theoretical potential for causing any level of immune response, will be excluded. Once the concept works and we see success, the intent is to open up the inclusion criteria and include all patients.

There are still unknowns with respect to persistence and redosing, but we feel confident that if we can get gene therapy working in Duchenne, we can put the smartest researchers on to figuring out these other issues.

On September 6, PPMD hosted a webinar on the Nationwide Children's microdystrophin gene therapy program, featuring Co-PI Dr. Jerry Mendell who discussed the different aspects of the trial. In the future, we will hold webinars on the other programs as they get closer to the clinic and entering into human trials.


Research Update

Last year, PPMD supported a grant to Dr. Eric Olson for CRISPR research. Specifically, the PPMD grant supported work around exploring and understanding any safely concerns associated with CRISPR. In addition, the grant requires comparing the new dystrophin created by microdystrophin gene therapy and CRISPR. This work is ongoing and will inform next steps with CRISPR. We are enthused by CRISPR, but the timeline is farther out than that of microdystrophin gene therapy, which we know concerns many families affected by a disease like Duchenne, where time is critical.

During our gene therapy webinar in August, CRISPR was discussed and compared to gene therapy. Reviewing the webinar and Q&A could be helpful in understanding the pros and cons of these new technologies.

Other Treatment Approaches

Research Update

While gene therapy continues to progress, there are many other therapeutic approaches that are being pursued. Close to twenty (20) companies presented their different drug progr... These approaches represented a variety of different targets and mechanisms of action. Some are in the pre-clinical phase, just developing their clinical trial protocol. Others are near completion, in Phase 2 or 3, moving toward FDA decision and hopefully towards approval.

Also at the Annual Conference, 40+ companies participated in PPMD’s Duchenne Drug Development Roundtable (DDDR) meeting. The camaraderie and energy that comes from our Annual Conference and all of the updates provided is always reassuring and reinforces how promising our Duchenne clinical trial pipeline is. And while the clinical trial process can be painfully slow, we are thankful for a full clinical pipeline.

PPMD will continue to identify obstacles in the drug development and clinical trial process, and with the help of leaders like those we assembled at this year’s DDDR meeting, seek solutions to accelerate therapies.

Choosing a Trial for You or Your Child

Research Update

If you or your child live with Duchenne, the decision to participate in a trial and identifying the best trial to participate in, can be overwhelming especially with 20 or more trials being conducted at any given time. PPMD’s patient registry, DuchenneConnect, has some great resources to help you think about this decision. DuchenneConnect’s video outlining the Types and Phases of Clinical Trials, explains how clinical trials are structured.

Other educational videos from our Registry help explain the clinical trial process. The Introductory Video focuses on important things to understand as one considers being in a trial, and explains the basics around What is a Clinical Trial?.

As you contemplate the array of options and wonder which one is for me/my child, DuchenneConnect’s clinical trial finder tool will help you selectively narrow down trials you might be eligible for by filtering trials by certain characteristics, such as ambulation status, mutation, and age.

Current and Planned Clinical Trials

Clinical Trials


Other Drug Programs

Research Update

While close to 20 drug programs were reported on during our Annual Conference, there are a considerable number of other programs in progress.

  • Tamoxifen, a well-studied Selective Estrogen Receptor Modulator, has been found in mdx mice to have an anti-fibrotic effect and assist in the repair of damaged muscles, both of which would be beneficial for Duchenne. A group in Europe will start a clinical trial of tamoxifen tentatively in the last quarter of 2017 or early 2018. The study will take place in Europe. This would be an example of repurposing a drug taking a generic drug and performing the necessary studies in the new indication to prove safety and efficacy. In the US, a group of researchers are considering a similar study, perhaps in a different age range, to add to the safety and efficacy story. The development pathway is slightly more complex with a repurposed drug and PPMD is actively convening experts to discuss and consider the best path forward.

  • Epicatechin, a key investment the community rallied in 2015 to help PPMD make, is being studied in a phase 1 safety study and is mid-way through dosing. Epicatechin has been found to improve muscle structure and function, induce production of muscle proteins, and induce mitochondrial biogenesis, all factors that could help ameliorate disease symptoms. There have been no safety issues in a previously studied cohort in Becker muscular dystrophy and we expect the same in Duchenne. We are looking forward to receiving the final study results.

  • Mallinckrodt Pharmaceuticals, who attended the Conference but did not present, has an IND under review at the FDA for an anti-inflammatory, Synacthen® Depot. They have received Fast Track Designation for the product and hope to be in the clinic soon.

As always, the PPMD team remains cautiously optimistic. We have 20+ clinical trials in progress, we have cutting edge gene therapy trials about to begin, and we are working diligently to identify the research gaps so that all patients can receive treatment, quickly and effectively.

Together, as a community, we can continue to make giant strides forward. Together, we will end Duchenne.

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