Neglected Tropical Diseases (NTDs) are a collection of parasitic and bacterial diseases that cause substantial illness (and many deaths) impacting over one billion people worldwide. The economic and scientific challenges of developing therapeutics have placed significant hurdles in the way of developing effective treatments for NTDs despite the acute need for them. The diversity of the pathogens implicated in NTDs, the relative complexity of their life cycles and their poor tractability in the lab have resulted in a lack of potential therapeutic targets and candidates. Tackling NTDs, therefore, requires an alternative approach.
In recent years the pharmaceutical industry has gradually shifted towards target-based high throughput screening to identify lead candidates due to their cost and scalability advantages over whole-cell, phenotypic assays. For many NTDs, however, target-based screens would likely be ineffective, as poor characterization of their metabolic pathways and annotations of their genomes often produce few, if any, active therapeutic targets. As a result, the majority of NTD lead identification has focused on phenotypic assays and, while many thousands of compounds have been tested for a couple of these diseases – in this case for Ebola and Chagas disease – this has only explored a small fraction of the potential therapeutic space for these and many other NTDs.
A team of dedicated chemists, biologists and computational scientists from Collaborations Pharmaceuticals, which targets NTD and rare diseases, have adopted an “in silico first” approach, applying a variety of machine learning techniques to identify novel and repurposed therapeutics.
Collaboration Pharmaceuticals’ approach to tackling this problem focused on repurposing existing high throughput screening (HTS) data for Ebola and Chagas Disease to create machine learning models which could screen libraries for potential active compounds, especially compounds previously approved by the US FDA for other diseases. To date, they have received three orphan drug designations from the FDA and are constantly striving to provide safe and efficacious treatments for those who need them most.