Overview

The Muscular Dystrophy Translational Research program in the Johnson Laboratory aims to advance therapeutic development across the muscular dystrophies by improving our understanding of the genetic causes and clinical progression of this class of disorders. The program has a focus on myotonic dystrophy and the limb girdle muscular dystrophies. There are multiple projects across the translational spectrum, as detailed below.

Myotonic Dystrophy

The lab focuses on the most severe form of myotonic dystrophy, congenital myotonic dystrophy, which begins at birth. Myotonic dystrophy is caused by an DNA repeat expansion that when transcribed into RNA sequesters RNA binding proteins leading to global dysregulation of RNA processing. Investigators are working on understanding the underlying RNA splicing changes associated with this phenotype through muscle samples and human cell lines. The aim of this project is to both understand the RNA splicing changes associated with the pediatric form as compared to the adult-onset form of this disease, how sequestration of unique RNA binding proteins leads to this specific RNA splicing profile, and how the splicing changes associated with the adult form of these disorder do not contribute to the unique congenital disease presentation.

The lab is also leading a genome wide association study to understand how other genomic variants alter the overall severity of this disorder. As part of this project, the lab focuses on families with large increases in the size of the repeat expansion between generations potentially caused by variants in DNA repair genes.

These efforts are supported by a 700 patient natural history study in adults with myotonic dystrophy that is coordinated by Dr. Johnson which will also develop clinical outcome assessments for this disorder. In addition there is a 100 patient natural history study in children with congenital myotonic dystrophy which similarly aims to develop clinical outcome assessments for these patients.

Limb Girdle Muscular Dystrophy

The Program supports the GRASP-LGMD consortium, a multicenter network aimed at developing clinical outcome assessments, resolving variants of unknown significance, and developing biomarkers in the limb girdle muscular dystrophies. There are multiple natural history studies being conducted in this program, as well as a study to resolve variants of unknown significance. In addition, the lab has ongoing efforts to develop muscle-based biomarkers in LGMD. Finally, there are projects to discover new genes for those patients without a clear diagnosis.

Other Projects

The Program also participates in ongoing natural history studies and clinical trials in facioscapulohumeral muscular dystrophy and spinal muscular atrophy.

Laboratory members