Drug repositioning in CNS

Chairs: M Davidson, C Canuso

While the research to design original, novel drugs based on the understanding of  the pathophysiology of mental illnesses continues, a parallel line of investigation tests drugs designed for non-mental illnesses indications, to treat mental illnesses.  The idea behind repositioning and repurposing is that a) drugs with similar chemical structure might have similar biological effects b) diseases with similar pathophysiology or similar molecular basis might respond to similar drugs c) most drugs affect more than one target (pathophysiological process, receptor). The impetus for repurposing derives on one hand from the lack of molecular and pathophysiologic understanding of this disease and on the other hand from the need to de-risk drug development.

Traditionally – in medicine in general and in psychiatry in particular – repositioning was the result of serendipitous but astute clinical observation of an unexpected benefit or expected or unexpected adverse effects.  Also epidemiological associations of a drug exposure with an unexpected benefit has occasionally let to successful reposition. More recently, repositioning has become systemic (not serendipitous) taking advantages of the latest technologies often  blurring the distinction between it and “de-novo”  drug development. Systematic computational analyses of transcriptomic (gene expression), GWAS large libraries of compounds are such examples. Candidates for repurposing can be drugs in preclinical development or active phases of clinical development (phase I-IV) or which are currently or have been on the markets.

In an attempt to facilitate the repositioning process collaborations have been established between governments the pharmaceutical industry (NCATS in the US and the New-Meds in Europe), not-for-profit foundations (Stanley Medical Research, NARSAD), for-profit (Biovista) and professional organizations (ECNP-Medication Chest).  Annual conferences (www.drugrepositioningconference.com) and journals (www.liebertpub.com/overview/drug-repurposing)have joined the effort.