Changing the Lives of Patients with

Myotubular and Centronuclear Myopathies (CNM)

Hierarchical Bayesian model of disease progression in centronuclear myopathy for demonstrating rare disease treatment efficacy with a small sample size

Monseur A, Boulanger B, Thielemans L, Paradis K, Freitag C, Carlin B, Seferian A, Servais L, and the Nathis MTM study group.

Clinical and genetic aspects of DNM2-related centronuclear myopathy; a retrospective, medical chart review to establish natural history

Aykanat A, Hoffmann S, Genetti C, Paradis K, Paterson H, AI-Husayni S, Lin B, Thielemans L, Freitag C, Beggs A

Rescue in XLCNM by genetic cross (proof-of-principle):

Cowling BS, Chevremont T, Prokic I, Kretz C, Ferry A, Coirault C, Koutsopoulos O, Laugel V, Romero NB, Laporte J. Reducing dynamin 2 expression rescues X-linked Centronuclear Myopathy. J Clin Invest. Mar;124(3):976-8.

Rescue in XLCNM, using ASO (developing translated approach):

Tasfaout H, Buono S, Guo S, Kretz C, Messaddeq N, Booten S, Greenlee S, Monia BP, Cowling BS*, Laporte J*. Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice. Nat Commun. 2017 Jun 7;8:15661.
*equal last and corresponding authors

Rescue by genetic cross in BIN1 form of disease (proof-of-principle):

Cowling BS*,Prokic I*, Tasfaout H, Rabai A, Humbert F, Rinaldi B, Nicot AS, Kretz C, Friant S, Roux A, Laporte J. Amphiphysin (BIN1) negatively regulates dynamin (DNM2) for normal muscle maturation. J Clin Invest, 2017 Nov 13. *equal first authors.

Innovative modelling approach by Dynacure/ISMS results in the 1st peer reviewed study on quantification of the centronuclear myopathy patient population:

I. Vandersmissen et al., An integrated modelling methodology for estimating the prevalence of centronuclear myopathy, Neuromuscular Disorders (2018)

Reducing dynamin 2 (DNM2) rescues DNM2-related dominant centronuclear myopathy:

Buono S, Ross JA, Tasfaout H, Levy Y, Kretz C, Tayefeh L, Matson J, Guo S, Kessler P, Monia BP, Bitoun M, Ochala J, Laporte J, Cowling BS. Reducing dynamin 2 (DNM2) rescues DNM2-related dominant centronuclear myopathy. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11066-11071.

Improving our understanding of DNM2 mutations in human disease:

Muñoz XM, Buono S, Koebel P, Laporte J, Cowling BS. Different in vivo impact of Dynamin 2 mutations implicated in Charcot-Marie-Tooth neuropathy or Centronuclear Myopathy. Hum Mol Genet. 2019 Oct 19. [Epub ahead of print] PubMed PMID: 31628461.

Development of therapies for Neuromuscular Disorders:

Cowling BS, Thielemans L. Translational medicine in neuromuscular disorders: from academia to industry. Dis Mod Mech.2020 13: dmm041434 doi: 10.1242/dmm.041434 Published 24 October 2019.

Antisense therapy for Centronuclear Myopathies:

Cowling BS, Guo S. Antisense oligonucleotide-mediated DNM2 targeting in centronuclear myopathies: from preclinical proof of concept towards clinical trials. Monographic special issue: Oligonucleotides & peptides – Chemistry today, TKS technoscience. 2019: 37(2), 68-70.