GALGT2 Gene Therapy - Viral gene transfer for GALGT2 as a surrogate gene therapy for Duchenne


Frequently Asked Questions (FAQs) about this study:


What stage is this research?


  • This research is clinical, meaning it has advanced to clinical trials involving people. An IND application has been approved by the FDA.
  • Funding for an initial trial of intramuscular injection of the virus (rAAVrh74.MCK.GALGT2) has been obtained.
  • IRB approval is pending. We anticipate enrolling the first patients in the intramuscular injection study in August, 2015.



What is the goal or purpose of this study?

  • The goal of this study is to introduce the GALGT2 Glossary Link gene into the body by using a viral Glossary Link vector (an adeno-associated virus, or AAV). Because the virus carries GALGT2 rather than a version of the dystrophin gene, it is a "surrogate" gene therapy.
  • GALGT2 encodes the Glossary Link protein GalNAc transferase (beta 1,4 –N-acetylgalactosamine galactosyltransferase). This is an Glossary Link enzyme that transfers a complex sugar Glossary Link molecule onto a few specific proteins, including dystroglycan.
  • Usually, GalNAc transferase is found only at the neuromuscular junction (NMJ), where some components of the dystroglycan-associated protein complex are different than elsewhere in muscle. Importantly, at the NMJ, utrophin is present instead of dystrophin.
  • In the mdx mouse, viral gene transfer of GALGT2 results in expression of GalNAc transferase across the entire muscle membrane (instead of just at the NMJ), as well as upregulation of utrophin across the entire muscle fiber.
  • In the mdx mouse, this expression can correct muscle functional deficits to the same degree as does microdystrophin gene expression. Furthermore, overexpression of GALGT2 corrects muscle pathology in mouse models of other muscular dystrophies, including LGMD2A and congenital muscular dystrophy (MDC1A).
  • This AAV viral vector is known not to cause disease. The vector includes a gene promoter that is specifically activated in muscle tissue, so the gene should not be significantly activated in other tissues. The AAV-delivered gene is not integrated into chromosomal Glossary Link DNA.
  • Because the GalNAc transferase is already expressed in patients, there should not be any immune response generated to the transferred gene's protein product.


Who is funding this study?

  • Development, preclinical testing, and the clinical trial have been funded by the NIH.


Who is eligible to participate in this study?

  • The first-in-human gene transfer trial will consist of intramuscular injections into the extensor digitorum brevis (EDB) muscle on the side of the foot in recently non-ambulant patients over the age of 9 years. A subsequent phase of the trial will consist of intravascular delivery in ambulant boys.


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

  • Each EDB muscle (foot) will receive an injection; one will be saline, and the other will contain the viral vector. Muscle biopsy will be performed on each EDB muscle at either 6 or 12 weeks after injection.


Where does this study take place?

  • The clinical trial will take place at Nationwide Children's Hospital (NCH) in Columbus, Ohio.
    • How many visits to the study site are necessary?
      • We anticipate that the study will require 13 visits to NCH over two years.
    • Can any visits be done locally?
      • No
    • Is there any funding to help pay for travel?
      • We will be seeking funding to help pay for travel.


Will I get paid for participating in this study?

  • No


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 initial intramuscular injection study are unlikely to be eligible for follow up vascular delivery studies, due to the expected development of antibodies to the viral capsid.
  • 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?

  • The initial first-in-human intramuscular injection study is necessary to confirm the expression of the GALGT2 gene in humans, and to assess the safety of this expression. This information is needed to proceed to a future efficacy trial.
  • There is no likelihood of personal benefit by participation in this initial clinical trial, but there may be other benefits. These include allowing you or your child to participate in the advancement of a new and promising therapy, and helping others by contributing to the better understanding of DBMD.


Where can I learn more about this study?