Pediatric Neuromuscular

Research topics

The main goal of our research is to develop new therapies for Duchenne and Becker muscular dystrophy (DMD and BMD) and other neuromuscular dystrophies which currently have no cure. DMD is the most common muscular dystrophy in children. DMD patients suffer from progressive muscle atrophy and weakness, lose independent ambulation by the age of 13 years and often die in their third decade.

Our laboratory focuses on understanding biochemical and molecular mechanisms leading to muscle dystrophy and the significant processes contributing to its secondary effects and disease progression, such as chronic inflammation and fibrosis. We are using diverse anti-inflammatory and anti-fibrotic agents and also combination therapies, to tackle the massive inflammation and fibrosis to improve outcomes in mouse models of DMD and of congenital muscular dystrophy (CMD). We also combined different novel strategies of gene therapy, small molecules and nanotechnology such as liposomes, exosomes and other nanoparticles to deliver drugs specifically to muscles. Diverse methodologies, including mouse models, human muscle biopsies, primary muscle satellite cells, and bioinformatics techniques are employed. We use novel high throughput sequencing (RNA-Seq) platform enabling us to identify novel genes that promote muscle regeneration and seek to extend the animal findings to humans. In addition to pure translational studies, biomarkers in our laboratory are evaluated as an aid to study Duchenne and Becker muscular dystrophy patients' physical activity and performance.

Figure 1. Model for the impaired regeneration mechanism in dy2J/dy2J mouse skeletal muscle (Yanay et al 2019).

Figure 2. Treatment with nano-liposomes (NSSL), remotely loaded with steroid decreased serum TGF-β and reduced diaphragm macrophage infiltration. In the long-term, NSSL-MPS demonstrated improved muscle strength and mobility compared to MPS as-is and induced lower tibia and lumbar vertebrae osteoporosis. (Turjeman and Yanay et al 2018)