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

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.

Recent publications include the results of a gene therapy clinical trial for myotubular myopathy (The Lancet Neurology 2023, see press release 2023/11/16), the development and characterization of new AAV capsids for more efficient transfer into skeletal muscle (Science Advances 2022), and the development of a gene therapy approach for acid ceramidase deficiency.

Recent publications

1. Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial.
   Shieh PB, Kuntz NL, Dowling JJ, Müller-Felber W, Bönnemann CG, Seferian AM, Servais L, Smith BK, Muntoni F, Blaschek A, Foley AR, Saade DN, Neuhaus S, Alfano LN, Beggs AH, Buj-Bello A, Childers MK, Duong T, Graham RJ, Jain M, Coats J, MacBean V, James ES, Lee J, Mavilio F, Miller W, Varfaj F, Murtagh M, Han C, Noursalehi M, Lawlor MW, Prasad S, Rico S. Lancet Neurology. 2023 Dec;22(12):1125-1139.
   
2. Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders.
   El Andari J*, Renaud-Gabardos E*, Tulalamba W, Weinmann J, Mangin L, Pham QH, Hille S, Bennett A, Attebi E, Bourges E, Leborgne C, Guerchet N, Fakhiri J, Krämer C, Wiedtke E, McKenna R, Guianvarc’h L, Toueille M, Ronzitti G, Hebben M, Mingozzi F, VandenDriessche T, Agbandje-McKenna M, Müller OJ, Chuah MK, Buj-Bello A*, Grimm D*. Science Advances. 2022 Sep 23;8(38):eabn4704. *Co-first and co-last authors.
   
3. 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.
   
   
4. 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.
   
   
5. 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.
   
   
6. 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. 
   
   
7. 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.

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