Repurposing medications for orphan diseases

Orphan genetic diseases are defined as those with global incidence of 1:1500-2500; however, in total, they affect ~10% of the world population. Subsequently, most orphan diseases are not targeted by pharmaceutical companies, as drug development is a long and expensive process. While development of new drugs is an important endeavor, we should explore possible novel indications to existing medications, i.e. drug repurposing. Advantages include reduced cost and regulation process for a drug already on the market (known safety profile), a broader product portfolio for pharmaceutical companies and for patients, who will also benefit from precision medicine. One of our projects involved the repurposing of eculizumab (Soliris) for CD55-deficiency, which causes life-threatening protein-losing enteropathy and venous thrombosis. We demonstrated a proof-of-concept beneficial effect and safety profile, and the positive long-standing effects of this treatment.

One of our current projects focuses on repurposing medications for read-through of premature terminations codons (PTCs), which account for ~11% of all disease-causing variants in humans. Our goal is to implement PTC suppression therapy to a larger cohort of patients with nonsense mutations, independent of the gene or disorder. This phenotype-based novel approach can broaden the implementation of PTC read-through therapeutics in genetic disorders. For this purpose, we established a phenotype-based registry for patients with PTC mutations. This will allow us to recruit a large cohort of patients with similar symptoms, each with their own culprit gene and genotype, and to tailor a research protocol to study outcomes under PTC read-through therapy with repurposing available medications.