Introduction

The use of cystic fibrosis transmembrane conductance regulator (CFTR) molecules for the treatment of rare genetic muscular diseases is the object of this patent, specifically targeted for sarcoglycanopathies, catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brody myopathy.

Technical features

Sarcoglycanopathies, catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brody myopathy  are rare inherited striated muscle diseases that lead to severe disability and are potentially lethal. Currently no treatment is available.  All three diseases are caused by the loss of function of a potentially active protein that is unable to retain its correct structure. To re-establish its function, this invention focuses on favouring the folding of the faulty protein by using molecules known as CFTR (Cystic fibrosis transmembrane conductance regulator) correctors, already selected for the treatment of cystic fibrosis.  Although on its own each disease is rare, the three put together affect a significant number of the population, notwithstanding the incidence of Brody myopathy is likely largely underestimated.

Currently this technology in the pre-clinical development phase. It efficacy has been proven through in vitro experimental models (cell lines and patient cells) and in animal models (in vivo and ex vivo).

Possible Applications

• Pharmacological treatment of rare inherited muscular diseases, currently without treatment: Sarcoglycanopathies, catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brody myopathy;
• Rare orphan disease treatment;
• Compounds are active on the cause of the disease, the defective protein, by causing it to fold correctly and move towards its normal active site;
• Small molecules are easy to synthesize, optimize and administer since they easily reach their target (heart and muscle).

Advantages

• Drug treatment for Sarcoglycanopathies;
• Drug treatment for catecholaminergic polymorphic ventricular tachycardia (CPVT);
• Drug treatment for Brody myopathy;
• Potential treatment for other diseases with the same pathogenetic mechanism.