Supplementary Materials

Supplementary Material for:

Gene Therapy Prolongs Survival and Restores Function in Murine and Canine Models of Myotubular Myopathy

Martin K. Childers,* Romain Joubert, Karine Poulard, Christelle Moal, Robert W. Grange, Jonathan A. Doering, Michael W. Lawlor, Branden E. Rider, Thibaud Jamet, Nathalie Danièle, Samia Martin, Christel Rivière, Thomas Soker, Caroline Hammer, Laetitia Van Wittenberghe, Mandy Lockard, Xuan Guan, Melissa Goddard, Erin Mitchell, Jane Barber, J. Koudy Williams, David L. Mack, Mark E. Furth, Alban Vignaud, Carole Masurier, Fulvio Mavilio, Philippe Moullier, Alan H. Beggs,* Anna Buj-Bello*

*Corresponding author. E-mail: (A.B.-B.); (A.H.B.); (M.K.C.)

Published 22 January 2014, Sci. Transl. Med.6, 220ra10 (2014)
DOI: 10.1126/scitranslmed.3007523

This PDF file includes:

  • Immune response profile in XLMTM dogs
  • Fig. S1. Pathology of muscles from myotubularin-deficient mice at 3 weeks of age.
  • Fig. S2. Systemic gene replacement therapy ameliorates pathological hallmarks of myotubular myopathy in skeletal muscles.
  • Fig. S3. Intravascular delivery of a lower dose of AAV8-Mtm1 in myotubularindeficient mice improves partially life span and body growth.
  • Fig. S4. Targeted myotubularin gene replacement therapy in XLMTM dogs increases the overall size of injected muscles.
  • Fig. S5. Targeted gene therapy with AAV8-MTM1 injected into the cranial tibialis muscle improves in vivo contractile response to repeated lengthening (eccentric) contractions in XLMTM dogs.
  • Fig. S6. In vivo strength measured 1 year after regional hindlimb infusion of AAV8-MTM1 in an XLMTM dog.
  • Fig. S7. Representative Western blot of myotubularin transgene expression in XLMTM dogs infused with AAV8-MTM1.
  • Fig. S8. Necropsy findings in the heart of an XLMTM dog 1 year after AAV8-MTM1 infusion.
  • Fig. S9. Humoral response specific to AAV8 and myotubularin in XLMTM dogs.
  • Fig. S10. Cellular response to AAV8 or MTM1 protein in XLMTM dogs.
  • Table S1. Quantified histological findings in dogs after intramuscular injection.
  • Table S2. Quantified histological findings in dogs after intravenous AAV.
  • Table S3. Quantified histological findings in autopsy tissue at 1 year after infusion.
  • Table S4. Innate immune responses after intramuscular or regional limb administration of AAV8-MTM1 in XLMTM dogs (dogs 1 to 6) and an untreated XLMTM dog (dog C).

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Other Supplementary Material for this manuscript includes the following:

  • Movie S1 (.mp4 format). Wild-type mouse (red tail) and myotubularin-deficient mouse (blue tail) treated with AAV8-Mtm1 (3 × 1013 vg/ml) at 6 months after injection (note the robust appearance, normal size, and activity of the treated Mtm1 KO mouse).
  • Movie S2 (.m4v format). XLMTM dogs (dogs 4 to 6) treated with AAV8-MTM1, two untreated XLMTM dogs, and a normal control dog at various times.

[Movies S1 and S2 ]