Generation 2.5 antisense drug
IONIS-DNM2-2.5Rx is an antisense drug designed to reduce the production of Dynamin 2 (DNM2) protein for the treatment of centronuclear myopathy (CNM). CNM is a group of rare congenital myopathies where cell nuclei are abnormally located in the center of the skeletal muscle cells. DNM2 reduction, either by genetic manipulation or antisense oligonucleotide treatment, improves muscle mass and muscle force in mouse models of main forms of CNM, and extends lifespan in the most severe form of CNM.
About Centronuclear Myopathy
CNM is a group of rare congenital myopathies where cell nuclei are abnormally located in the center of the skeletal muscle cells. Clinical features include muscle weakness, hypotonia and muscle atrophy, ranging from severe to mild. There are three main forms of CNM. X-linked CNM (XL-CNM, also known as myotubular myopathy) is a life-threatening form of CNM with a neonatal disease onset caused by mutations in myotubularin (MTM1); autosomal recessive CNM (AR-CNM) is a less severe form with a neonatal to childhood onset caused by mutations in amphiphysin 2 (BIN1); autosomal dominant CNM (AD-CNM) is a mild form of CNM with likely an adulthood onset due to mutations in dynamin 2 (DNM2). Estimated incidence of XL-CNM is 1 in 50,000 male live births. AR-CNM and AD-CNM may have similar incidence, but prevalence is higher due to longer survival.
Buono, S. et al. “Reducing dynamin 2 (DNM2) rescues DNM2-related dominant centronuclear myopathy” Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11066-11071. Epub 2018 Oct 5.
Tasfaout, H. et al. “Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice” Nature Communications volume 8, Article number: 15661 (2017).
* Safety and efficacy have not been evaluated by any regulatory authorities for the indications described.