Myotonic Dystrophy
This slowly progressive degenerative muscle disease, affecting as many as 60,000 individuals in the USA, is
the second target disease for which 4s3 Bioscience has generated convincing in vivo proof-of-concept data.
DM1, the most common adult muscular dystrophy is caused by mutational expansion of CTG repeats in the 3’
untranslated region of the DMPK gene. As a result, hairpin expanded poly(CUG) RNA has been shown to interfere
with alternative splicing of certain pre-mRNAs by locking up Muscleblind (MBNL1), an essential factor in the
expression of adult forms of the expressed proteins. Most of the dozen or so known mispliced pre-mRNAs are
closely linked to specific myotonic dystrophy symptoms or pathology, eg., cardiac (and skeletal) muscle
troponin T (cTnT), the insulin receptor (IR) and the muscle-specific chloride ion channel (ClC-1). Patients
with myotonic dystrophy are most often diagnosed as juveniles or young adults with progressive muscle weakness,
respiratory failure, myotonia and many have diabetes. Slow, steady progression of the disease leads to
ambulatory and respiratory failure in middle age. 4s3 Bioscience has pursued a therapeutic strategy of replacing
the MBNL1 protein with an active truncated version, conjugated to our 3E10Fv antibody. Additional in vivo
studies are on-going and IND-enabling manufacturing / preclinical studies have been inititated.