The standard drug discovery pipeline comprises target discovery and validation, screening or designing chemicals with biological activity, evaluate their absorption, distribution, metabolism, excretion and toxicity and optimizing the drugs, assessing the efficacy and toxicity in clinical trials and final obtaining the approval. This is a very large process that takes around 12 to 17 years, involving a huge amount of money. Along the years, the investment in drug discovery worldwide has increased, but the number of drugs approved did not follow this trend. Therefore, there is an urgent need of finding other strategies to discover new drugs, like drug repositioning. Drug repositioning finds new uses for existing drugs. Recycling compounds to a new indication reduces the time and money needed, as well as the risk of failure in late-stage clinical trials due to safety reasons. A well-known example is sildenafil (Viagra), which was initially developed to treat angina and was finally approved for erectile disfunction.
In this work, our group, together with SOM biotech, followed a drug repositioning strategy with the aim of finding new compounds for the treatment of transthyretin amyloidosis. Transthyretin amyloidosis is the designation given to a group of slowly progressive, eventually fatal, diseases, caused by the aggregation of transthyretin. These diseases affect different organs and tissues, resulting in distinct clinical phenotypes. In this context, we discovered tolcapone, a drug approved by the United States Food and Drug Administration (FDA) as a coadjuvant for Parkinson’s disease and that has the capacity to cross the blood-brain barrier, constituting a powerful option for fighting brain-related transthyretin amyloidosis.