People with myotubular Myopathy have a mutation in the gene MTM1. In consequence, either no enzyme myotubularin is produced or only very little or that myotubularin that is produced cannot fulfill the function of the “normal” myotubularin.
Thus, a possible approach for a therapy would be to add this enzyme (myotubularin) to the muscle cells from outside. This is called enzyme replacement therapy. The approach presented here works differently:
Apparently, the enzyme myotubularin controls the activity of another enzyme in muscle cells, called dynamin. If there is no or only little myotubularin in the muscle cells then the concentration of dynamin gets to high. The here presented approach is based on the idea to lower the concentration of dynamin.
Belinda Cowling presented this idea at the conference #TogetherEvenStronger 2016 in Frankfurt. She could show that mice with a mutation in the MTM1- gene and lowered dynamin production were almost as strong as completely healthy mice. Belinda issued a short article on all this in our 2016 newsletter (page 3)
In 2016 in cooperation with the researchers at the IGBMC a start-ap company called Dynacure has been founded. Dynacure has teamed up with Ionis Pharmaceuticals (Carlsbad, USA) which will provide its unique expertise in antisense chemistry. Antisense oligopeptids are small pieces of DNA that can specifically fine-tune genes of interest, such as DNM2 in the present application. (Further reading: wikipedia)
Members of the Myotubular Trust and of ZNM – Zusammen Stark! e. V. have visited Dynacure in March 2017 and were informed about recent achievements. Here is a short report.
People with a centronuclear myopathy caused by a mutation in the gene DNM2 usually produce a form of Dynamin that is more active a s normal dynamin. Also for these people this therapeutic approach could lead to an improvement of their health.
“In addition, we have shown that targeting DNM2 is beneficial to both myotubular and centronuclear myopathies (BIN1-related). BIN1-treated mice are able to walk around the cage, and maintain whole body strength up until at least 18 months of age, nearly a full lifespan for a mouse, indicating targeting DNM2 may be a valid therapy for several forms of centronuclear myopathies.” say Belinda Cowling. This ongoing work is supported by a grant from the Myotubular Trust”
Presentations at family conferences
Belinda Cowling, “How reducing the protein dynamin 2 improves the symptoms of myotubular myopathy”
Link to Belinda’s presentation (pdf)
Presentation as video:
Belinda S. Cowling, Thierry Chevremont, Ivana Prokic, Christine Kretz, Arnaud Ferry, Catherine Coirault, Olga Koutsopoulos, Vincent Laugel, Norma B. Romero, and Jocelyn Laporte, Reducing dynamin 2 expression rescues X-linked centronuclear myopathy J Clin Invest.2014;124(3):1350–1363. doi:10.1172/JCI71206, http://www.jci.org/articles/view/71206/pdfHichem Tasfaout,Suzie Buono, Shuling Guo, Christine Kretz, Nadia Messaddeq,
Sheri Booten, Sarah Greenlee, Brett P. Monia, Belinda S. Cowling & Jocelyn Laporte, Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice,Nature Communications 8, Article number: 15661 (2017) doi:10.1038/ncomms15661 https://www.nature.com/articles/ncomms15661
Further reading and used sources:
Further therapeutic approaches are listed and explained on this page