News from 2017 World Muscle Society: Part 2

Annie Kennedy and Kathi Kinnett from the PPMD team recently attended the 22nd International Annual Congress of the World Muscle Society and have been reporting back the latest updates related to Duchenne. Below is the second and final update from this year's WMS meeting. Click here to read Part 1 of these updates.

SRP-4053 Induces Exon Skipping Leading to Sarcolemmal Dystrophin Expression in Duchenne Muscular Dystrophy Patients Amenable to Exon 53 Skipping

We were excited to see that the London group, let by Francesco Muntoni, presented data around the European study (SRP-4053) testing the safety, efficacy, and pharmacokinetics of using phosporodiamidate morpholino oligomer (PMO) technology to skip exon 53. The trial, SKIP-NMD, is a 2-part double blind placebo controlled trial of 25 ambulatory boys ages 6-15 y/o and 24 controls. 

  • All 25 patients showed an increase in new dystrophin measured by Western blot
  • Showed an increase in exon 53 skipping in all 25 patients
  • Showed an increase in new dystrophin in the sarcolemma, the sheath surrounding each of the muscle fibers
  • SRP-4053 (golodirsen) is the second PMO to demonstrate the ability to increase dystrophin in humans

We will keep you updated when further data is available.

Rimeporide: Safety, Tolerability and Pharmacokinetic Results from a Phase Ib Study in Duchenne Boys as Well as Exploratory Biomarkers

In an effort to reduce early death due to cardiomyopathy, the Italian group, led by Drs. Muntoni and Gidaro, are evaluating the safety of Rimeporide in Duchenne. Rimeporide is a potent NHE-1 inhibitor that has demonstrated promising data on skeletal muscle function, fibrosis, and inflammation in skeletal, cardiac, and diaphragm muscle in the mdx mouse. In hamsters and the mdx mice, there was a reduction in mortality, cardiac pathology, and fibrosis. In the human study, 20 patients, ages 6-14 years old, are participating in an open label dose finding study, exposed to 4 doses (ranging between 50m – 600 mg/day) or 4 weeks. To date, 15 patients have finished the first 3-dosing cohorts and no safety signals have been noted. Known biomarkers indicating inflammation and fibrosis, as well as novel translational markers, are being collected and evaluated. The study is projected to end December 2017.


Repurposing Tamoxifen for Severe Myopathies: from Preclinical Evaluation in Animal Models to Clinical Trials in Duchenne

A group from Switzerland, France, and Israel are evaluating the impact that tamoxifen, a drug that has been used to treat breast cancer, might have on cardiac and respiratory dysfunction in Duchenne. The study TAMDMD, is an ongoing random placebo controlled trial currently evaluating 84 patients, ages 6-10 years old,  in 11 European centers in 8 countries.  Compassionate use of tamoxifen for 3 boys in Israel has shown the drug to be, so far, safe and efficacious. In addition, this work has revealed the role of the estrogen signaling pathway may have in  disease modification, which may lead to the development of a different line of drugs that may impact this pathway. This study is ongoing.


Effects of Long-Term Eteplirsen Treatment on Upper Limb Function in Patients with Duchenne Muscular Dystrophy: Findings of 2 Phase 2 Trials

The Nationwide Children’s Hospital Team evaluated 12 patients who had participated in both the 201 and 202 arms of the eteplirsen study, which led to the accelerated approval of Exondys 51. All 12 patients demonstrated relative stability or minimal decline of all measures of upper limb function.


Injection Site Reactions as a Consequence of Long-Term Subcutaneous Administration of Drisapresen in Duchenne 

The European group, led by Dr. Niks and Goemans, studied the long-term injection site reactions (ISR’s) of 49 patients who had received treatment between 15 and 42 months. All of the 49 patients developed ISR’s. Typical ISR’s included redness and pigment (skin coloration) changes, which were then followed by thinning of the skin, sclerosis (or destruction) of the muscle and induration (or inward dips) of the muscle, destruction of the fat layer (lipoatrophy), calcification, and slow healing ulcers were seen in a significant number of patients. Some injection sites were painful and several patients experienced hair loss. Importantly, in many patients, these changes were noted to continue to progress after the injections had stopped the injections or had switched to IV administration.  Skin biopsies showed inflammation, or fibrosis and calcification of the skin and muscle at the injection site, and MRI of the sites showed severe loss of subcutaneous fat. While ISR’s have been shown in other diseases using subcutaneously injected antisense oligonucleotide, this first report of severe, irreversible injection site reactions resultant of subcutaneous 2OMePS AONs. The conclusion of this study: these findings limit the long term use of this treatment in Duchenne, as well as potentially in other diseases.  

PTC – Industry Sponsored Symposium

Growing up With Duchenne: How should we be caring for our patients and measuring the benefits of our treatments now and in the future?

Yann Pereon, France; Craig Campbell, Children’s Hospital LHSC, Canada; Imelda de Groot (Netherlands); Rosaline Quinlivan (UK)


The purpose of this panel was to highlight challenges and opportunities for individuals with Duchenne as they transition from pediatric to adult care, while also providing the clinicians present an opportunity to better understand the data behind ataluren and whether it might be appropriate for their patients.


Dr. Craig Campbell opened the session with a description of the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) considerations for clinical decisions and adoption of evidence. They include a methodology for evaluating the consistency of the totality of the evidence for clinical decision making. GRADE is comprised of 4 domains of evaluation of treatment benefits:

  • Grounded in evidence
    • Focus less on effect size and more on consistency of the evidence
  • Benefit/Risk profile
    • Safety vs. harm
  • Patient Preferences
    • Values, preferences, feasibility, costs
  • Disease characteristics
    • Consistent phenotype, unmet need

He then provided an overview of ataluren and discussed commercial availability in Israel, South Korea, and Europe. Dr, Campbell then provided a review of the Phase 2b study design and results, the ACT DMD study design and results, and the 3 meta-analyses that were conducted. His presentation concluded with the open-label extension data, Study 019.


Imelda de Groot then presented on the DBMD Care Considerations and delivery of care through centers of excellence. Followed by a presentation by Dr. Rosaline Quinlin focused on preparing young people with Duchenne ages 14-25 for adulthood. She began her talk with the question, “Are we ready for pediatrics with Duchenne to walk into adult care?” and concluded her talk with a list of topics that the care providers in the UK recommend be addressed by Duchenne care providers. The key aspects of transition she identified were:

  • Inform the young person & family of transition plan by 12 years
  • Foster independence and agree goals
  • Start involving the young person in a transition plan from 13-14 years
  • Link with social care and education
  • Involve young people in service design
  • Treat the yound person as an equal partner
  • Transition coordinator
  • Peer support
  • Support the young person to make their own decision
  • Have a health plan/ passport, review annually

She also underscored the recommendation from young adults with Duchenne who participated in the that the ENMC Workshop on Transition that advocacy for and by adults with Duchenne was needed.


The session ended with a question and answer period on a wide variety of topics.


Previous Updates:

News from 2017 World Muscle Society: Part 1

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