Neuromuscular diseases and gene therapy team

The team aims to develop innovative treatments for neuromuscular diseases based on gene transfer and understanding of pathophysiological mechanisms. It works in particular on congenital muscle diseases such as myotubular myopathy.

The team’s researchers

Ana Buj-Bello
MD, PhD, EMBA

Team leader
Research Director Inserm

Expertise: neuromuscular diseases, congenital myopathies, neurosiences, gene therapy

0000-0003-0450-9464

Andrea Burgo
PhD,

Senior lecturer
Université d’Evry /Paris Saclay

Expertise:
neurodegenerative diseases, vesicular traffic, imaging
0000-0002-0270-5448

Janek Hyzewicz, PhD

Senior lecturer Université d’Evry /Paris Saclay

Expertise: neuromuscular diseases, animal physiology, proteomics

0000-0002-2333-9336

Martina Marinello, PhD

Researcher

Expertise: neurosciences, gene therapy, imagery
0000-0001-9059-3310

Edith Renaud-Gabardos, PhD

Researcher

Expertise: vectorology, neuromuscular diseases

0000-0003-4209-2559

The team’s projects

The team performed pioneering preclinical work in the development of gene therapy for myotubular myopathy which resulted in an international phase I/II clinical trial. Its translational research is currently focused on the exploration and optimization of new therapeutic approaches for orphan neuromuscular diseases using AAV vector technology and genome editing.

Among recent publications, a first proof of principle for a gene therapy for Steinert’s disease by the reduction of CTG triplets using the CRISPR / Cas9 system.

Recent publications

  1. Lo Scrudato M, Poulard K, Sourd C, Tomé S, Klein AF, Corre G, Huguet A, Furling D, Gourdon G, Buj-Bello A. Genome Editing of Expanded CTG Repeats within the Human DMPK Gene Reduces Nuclear RNA Foci in the Muscle of DM1 Mice. Molecular Therapy. 2019 Aug 7;27(8):1372-1388.

  2. Mariot V*, Joubert R*, Hourdé C, Féasson L, Hanna M, Muntoni F, Maisonobe T, Servais L, Bogni C, Le Panse R, Benvensite O, Stojkovic T, Machado PM, Voit T*, Buj-Bello A*, Dumonceaux J. Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches. Nature Communications. 2017 Nov 30;8(1):1859. *Equal contribution.

  3. Mack DL, Poulard K, Goddard MA, Latournerie V, Snyder JM, Grange RW, Elverman MR, Denard J, Veron P, Buscara L, Le Bec C, Hogrel JY, Brezovec AG, Meng H, Yang L, Liu F, O’Callaghan M, Gopal N, Kelly VE, Smith BK, Strande JL, Mavilio F, Beggs AH, Mingozzi F, Lawlor MW, Buj-Bello A*, Childers MK*. Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs. Molecular Therapy. 2017 Apr 5;25(4):839-854. *Co-last authors.

  4. Childers MK, Joubert R, Poulard K, Moal C, Grange RW, Doering JA, Lawlor MW, Rider BE, Jamet T, Danièle N, Martin N, Rivière C, Soker T, Hammer C, Van Wittenberghe L, Lockard M, Guan X, Goddard M, Mitchell E, Barber J, Williams JK, Mack DL, Furth ME, Vignaud A, Masurier C, Mavilio F, Moullier P, Beggs AH, Buj-Bello A. Gene Therapy Prolongs Survival and Restores Muscle Function in Murine and Canine Models of X-linked Myotubular Myopathy. Science Translational Medicine, 2014 Jan 22;6(220):220ra10. 

  5. Joubert R, Vignaud A, Le M, Moal C, Messaddeq N, Buj-Bello A. Site-specific Mtm1 mutagenesis by an AAV-Cre vector reveals that myotubularin is essential in adult muscle. Human Molecular Genetics. 2013 May 1;22(9):1856-66.

Main funding partners