Introduction

The invention concerns molecules optimized for the treatment of type 2 dominant osteopetrosis, which act on the selective reduction of the mutated protein compared to the normal one.

Technical features

The CLCN7-dependent ADO2 is a disease characterized by the absence of function of bone cells called osteoclasts, which affects 5 individuals out of 100,000, and is caused by the mutation of a gene (CLCN7), essential for the function of osteoclasts.  This pathology is currently untreated. In this context, a team of researchers from the University of L’Aquila developed siRNAs optimized for the treatment of ADO2 CLCN7-dependent disease, which act on the selective reduction of the mutated protein compared to the normal one. The siRNA molecules developed have proved to be highly specific, eliminating at least 80% of the transcript of the mutated gene, restoring the function of the osteoclasts, and thus creating a situation similar to the normal functioning of the cells, and an improvement in the symptoms of the disease.

Possible Applications

• Therapy of type 2 autosomal dominant osteopetrosis (ADO2) caused by mutation of the CLCN7 gene (ADO2 CLCN-dependent).

Advantages

• Potential unique cure for the genetic pathology ADO2 CLCN-dependent. At present affected patients receive exclusively palliative therapies. The invention could cure the disease by giving patients a better, if not normal, quality of life;
• The design of the molecule developed is unique and can be applied to virtually all mutations involved in ADO2;
• Extension to additional active siRNAs against ADO2 mutations.