EXON 2 SKIPPING - To induce Internal Ribosomal Entry Site (IRES) activation in Duchenne patients with Exon 2 Duplications


Frequently Asked Questions (FAQs) about this study:


What stage is this research?

  • This research is pre-clinical, meaning it has not advanced to clinical trials involving people yet.  


What steps need to be completed before moving into a clinical trial?

  • Completion of IND-enabling in-life toxicity studies in mice (now underway).


What is your best estimate for the length of time it will take to move this research into clinical trials?

  • 9 months.


What is the goal or purpose of this study?

  • The goal of this study is to induce skipping of either one of both copies of exon 2 in patients with exon 2 duplications.
  • We intended to induce exon skipping by the use of a virus carrying several copies of a modified small nuclear RNA (U7snRNA) targeted to exon 2, where it interferes with splicing.
  • Skipping of one copy of exon 2 will be expected to result in a wild-type DMD transcript and expression of a full-length dystrophin Glossary Link protein.  Skipping of both copies of exon 2 will be expected to result in the activation of an IRES in exon 5 that results in the production of a highly functional version of the dystrophin protein.


Who is funding this research?

  • The preclinical development of this study has been funded by CureDuchenne.  Funding for the clinical trial has not yet been obtained.


Who would be eligible to participate in this study?

  • The final enrollment criteria are not set, but we anticipate enrolling ambulate patients who carry a duplication of exon 2.


What would I have to do if I decide to participate in this study?

  • This study will involve frequent visits to Nationwide Children’s Hospital.
  • Delivery of the Glossary Link vector will likely require sedation and delivery to both legs via a catheter.
  • Muscle biopsies before and 12 weeks after vector delivery will be required.


How long will this study last, and will I have access to the drug/treatment once the study has ended?

  • The study will require follow up for two years after injection. 
  • Patients who participate in the trial are unlikely to be eligible for later Glossary Link gene delivery with the same vector, due to the expected development of antibodies to the viral capsid.  However, animal studies suggest that genes delivered by AAV viruses will last for years. 
  • If the treatment were to be approved by the FDA, plasmapheresis to clear anti-AAV antibodies may allow future treatment, although this cannot be guaranteed at present.


Why should I consider participating in this study?

  • Patients who naturally express the IRES-driven isoform of the dystrophin protein walk in to their seventh decade.
  • Studies in an animal model of exon 2 duplication DMD show that skipping can be done very efficiently with the virus.


Where can I learn more about this study?