Worldwide approximately 400 million people are affected by orphan diseases. Orphan diseases are defined by their low prevalence and therefore a low number of patients. In the US a disease is considered to be rare when it affects less than 200000 patients, which reflects a prevalence of around 7 in 10000 citizens. Treatments for these conditions - of which there are around 5000-8000 - are however few and far between, amounting to around 500 drugs with a marketing approval for an orphan disease in the US. The need for new therapies can therefore be clearly seen. Coupled with the fact that an orphan drug can generate up to 818 million dollars in revenue over its competition-free lifespan, a trend can be seen where pharma’s focus is shifting towards rare disease treatments.<br/>A second recent trend is the repurposing of approved compounds. Especially the reduction of drug development costs by repurposing safe and approved compounds is a very beneficial aspect for the rare disease community, whose biggest problem is the low return on drug development costs because of the low number of patients.<br/>To bring all these aspects together and facilitate a systematic search for repurposing candidates for orphan diseases, we developed a workflow which combines several databases and triangulates between the disease, its target and approved drugs for this target. This way we are able to find previously unnoticed associations between orphan diseases and approved drugs.<br/>We start out with information on orphan diseases from Orphanet (a platform for orphan diseases), connect the diseases to their respective targets in DisGeNET (which we access through the Open PHACTS Discovery Platform), and connect the targets to approved drugs through DrugBank (a database with drug data and drug target information). The results of this triangulation are associations between diseases and approved drugs, comprised of previously known and more importantly also new associations. Currently we are working on streamlining the analysis of these associations so as to minimize the manual curation needed to arrive at viable repurposing candidates.               <br/>For some of the roughly 8000 orphan diseases, drug repurposing is the only hope of gaining access to approved therapeutics. The abovementioned method is a systematic approach that creates value for the patient community as well as for the pharma industry.

Triangulation of repurposing candidates for orphan diseases

255th National Meeting (2018)

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