Pathophysiology of Striated Muscles

Description

Our group studies the cellular and molecular mechanisms underlying selected pathologies of cardiac and skeletal muscles with the aim to identify and develop novel therapeutic strategies to fight these rare diseases.Our efforts are devoted to clarify the pathogenic consequences of protein misfolding in sarcoglycanopathy, Brody disease and catecholaminergic polymorphic ventricular tachycardia (CPVT). We are also interested in understanding the molecular basis driving cardiac growth and the impact of these processes on the development of congenital and adult cardiovascular diseases. The study of heat stroke and of skeletal muscle atrophy as consequence of disuse (microgravity, ageing and bed rest) are two other topics of our group. To accomplish these tasks, we use cellular models, primary myogenic cells from healthy and affected subjects as well as mouse and zebrafish models of the diseases.

Italian patent 0001414647 (2015)

US patent 9,987,256 B2 (2018)

WO2014086687 A1 (EU pending)

EP18305018 (11.01.2018, pending)

 

5 recent publications

  • Carotti M., Marsolier J., Soardi M., Bianchini E., Gomiero C., Fecchio C., Henriques S.F., Betto R., Sacchetto R., Richard I., Sandonà D. Repairing folding-defective α-sarcoglycan mutants by CFTR correctors, a potential therapy for Limb Girdle Muscular Dystrophy 2D.  Hum Mol Genet. (2018) 27(6):969-984
  • Bianchini E., Fanin M., Mamchaoui K., Betto R., Sandonà D. Unveiling the degradative route of the V247M α-sarcoglycan mutant responsible for LGMD-2D. Hum Mol Genet. (2014) 23(14):3746-58
  • Furlan S, Mosole S, Murgia M, Nagaraj N, Argenton F, Volpe P, Nori A. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio. J Muscle Res Cell Motil. 2016 Apr;37(1-2):27-39.
  • Scardigli M, Müllenbroich C, Margoni E, Cannazzaro S, Crocini C, Ferrantini C5, Coppini R, Yan P, Loew LM, Campione M, Bocchi L, Giulietti D, Cerbai E, Poggesi C, Bub G, Pavone FS Sacconi L. Real-time optical manipulation of cardiac conduction in intact hearts. J Physiol. 2018 Jul 10. doi: 10.1113/JP276283. [Epub ahead of print]
  • Liu B, Walton SD, Ho HT, Belevych AE, Tikunova SB, Bonilla I, Shettigar V, Knollmann BC, Priori SG, Volpe P, Radwański PB, Davis JP, Györke S. Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin-Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia. J Am Heart Assoc. (2018) 7(10). pii: e008155. doi: 10.1161/JAHA.117.008155.

Grants

  • AFM (Association française contre les myopathies): “Small molecule-based therapy for sarcoglycanopathies. Assessment of efficacy and tolerability in novel animal models”
  • ITALIAN TELETHON: “Small molecules to rescue folding-defective sarcoglycans: in vivo assessment of novel therapeutic strategies.”
  • MDA (Muscular dystrophy association): “Novel zebrafish models of sarcoglycanopathy. Swimming toward a cure.”
  • UNIVERSITY OF PADOVA: “Maturazione nel Reticolo Endoplasmatico di proteine di membrana del muscolo scheletrico”
  • ASI (Agenzia Spaziale Italiana)

 

Links

rare diseases: 

 

pathogenic consequences of protein misfolding: 

 

molecular basis driving cardiac growth: 

 

skeletal muscle atrophy: 

 

mouse and zebrafish models of the diseases: