IN VITRO AND IN VIVO STUDY OF SALBUTAMOL, A POTENTIAL THERAPEUTIC AGENT FOR SPINAL MUSCULAR ATROPHY

Spinal muscular atrophy (SMA) is caused by an insufficient level of the SMN protein. Progress in SMA research has raised the possibility to undertake therapeutic strategies aimed at increasing SMN protein by enhancing the expression of the SMN2 genes present in SMA patients. Preliminary data of a clinical and an in vitro study suggest that salbutamol, a beta2-adrenergic agonist, may be a good candidate for the pharmacological treatment of SMA patients. We propose here to perform a molecular study of the action of salbutamol on the expression of the SMN2 genes. In parallel we will perform an open pilot trial in SMA type II patients to whom oral salbutamol will be given for 6 months. We will assess the effect of this drug on motor function, muscle strength and synthesis of functional SMN2 gene products in blood and in oral mucosal cells. The present project may provide preliminary evidence on whether salbutamol is effective in improving motor function in SMA patients and whether a correlation can be established between the clinical and molecular data. The data obtained in the proposed project should provide the basis for the design of a large double-blind placebo-controlled trial with salbutamol.