ABOUT US

Our team focuses on the development and evaluation of novel strategies to correct genetic defects that affect the neuromuscular system. We are particularly interested in finding a cure for congenital muscular diseases, such as myotubular myopathy. Our research concentrates on two main areas:

- AAV-mediated gene replacement therapy: the goal is to develop novel viral vectors, perform preclinical studies in animal models and clinical trials in patients.

- Genome editing: gene targeting at specific sites of the genome constitutes a promising approach for the in situ correction of a mutated gene and can be achieved by engineered nucleases such as the CRISPR/Cas9 system. We are using this approach to correct genetic defects that affect the musculature.

HIGHLIGHTS

M. K. Childers, R. Joubert, K. Poulard, C. Moal, R. W. Grange, J. A. Doering, M. W. Lawlor, B. E. Rider, T. Jamet, N. Daniele, S. Martin, C. Riviere, T. Soker, C. Hammer, L. Van Wittenberghe, M. Lockard, X. Guan, M. Goddard, E. Mitchell, J. Barber, J. K. Williams, D. L. Mack, M. E. Furth, A. Vignaud, C. Masurier, F. Mavilio, P. Moullier, A. H. Beggs, and A. Buj-Bello. Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy. Sci Transl Med, 6(220):220ra10, Jan 2014. [PubMed:24452262].

R. Joubert, A. Vignaud, M. Le, C. Moal, N. Messaddeq, and A. Buj-Bello. Site-specific Mtm1 mutagenesis by an AAV-Cre vector reveals that myotubularin is essential in adult muscle. Hum. Mol. Genet., 22(9):1856-1866, May 2013. [PubMed:23390130].

M. W. Lawlor, D. Armstrong, M. G. Viola, J. J. Widrick, H. Meng, R. W. Grange, M. K. Childers, C. P. Hsu, M. O'Callaghan, C. R. Pierson, A. Buj-Bello, and A. H. Beggs. Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy. Hum. Mol. Genet., 22(8):1525-1538, Apr 2013.  [PubMed:23307925].

J. J. Dowling, R. Joubert, S. E. Low, A. N. Durban, N. Messaddeq, X. Li, A. N. Dulin-Smith, A. D. Snyder, M. L. Marshall, J. T. Marshall, A. H. Beggs, A. Buj-Bello, and C. R. Pierson. Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models. Dis Model Mech, 5(6):852-859, Nov 2012. [PubMed:22645112].

L. Al-Qusairi, N. Weiss, A. Toussaint, C. Berbey, N. Messaddeq, C. Kretz, D. Sanoudou, A. H. Beggs, B. Allard, J. L. Mandel, J. Laporte, V. Jacquemond, and A. Buj-Bello. T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase. Proc. Natl. Acad. Sci. U.S.A., 106(44):18763-18768, Nov 2009. [PubMed:19846786].

A. Buj-Bello, F. Fougerousse, Y. Schwab, N. Messaddeq, D. Spehner, C. R. Pierson, M. Durand, C. Kretz, O. Danos, A. M. Douar, A. H. Beggs, P. Schultz, M. Montus, P. Denefle, and J. L. Mandel. AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis. Hum. Mol. Genet., 17(14):2132-2143, Jul 2008. [PubMed:18434328].

SUPPORT

• European Commission – Horizon 2020 – MYOCURE project, H2020-PHC-14-2015
• Myotubular Trust
• ATIGE, Genopole d’Evry