Strivastava PK, van Eyll J, Godard P, et al. Nature Communications, 9 (2018): 3651.
A recent article titled “A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target,” used the big data approach to discover a novel target for epilepsy.
- Epilepsy is a neurological disorder that is characterized by spontaneous seizures.
- The first line of treatment for epilepsy is anti-epileptic drugs. Unfortunately, approximately one-third of people with epilepsy live with uncontrolled seizures because no available treatments work for them. Current drugs are also associated with side effects.
- One reason for the lack of novel targets in epilepsy is that, unlike drugs for diseases like cancer, it is difficult to validate targets in early stages of drug development.
- Also, drug discovery is typically a slow process. It takes years for scientists to find a potential target in the brain, a molecule that affects the target, and then validate its safety and activity in animal and human studies.
Description of Study
- In the current study, scientists explore a new framework of drug discovery called Causal Reasoning Analytical Framework for Target discovery (CRAFT).
- The CRAFT method is unique because it considers genes that are expressed specifically in the epileptic brain and are correlated with seizure activity.
- In general, the causes of epilepsy can be genetic or acquired. In this paper, as a starting point, the scientists chose to apply CRAFT for acquired epilepsies.
- Eventually, the aim was to come up with leads for receptors on cell membranes that could act as targets for new drugs.
Summary of Study Findings
- By applying this framework, the authors were able to come up with “modules” of genes that were either over-expressed or under-expressed in epilepsy.
- A receptor that was found to be promising using the CRAFT method was Csf1R.
- This receptor was chosen for further testing because of the availability of a compound PLX3397 that acts on Csf1R.
- In line with genetic studies, the scientists found that targeting Csf1R had anti-epileptic properties in three, pre-clinical, animal models of epilepsy.
What does this mean?
- As opposed to the much longer timeline of typical drug discovery, the entire study took about two years due to the collaboration of pharmaceutical industry and academic scientists.
- More experiments in animals and humans will need to be done to confirm that the receptor Csf1R is a suitable target for anti-epileptic drugs. This is the first time that a genetic study of this scale was applied to find novel drugs for epilepsy.
- Although the authors of this study applied CRAFT to epilepsy, in theory this method could be applied to any neurological disorder.
Supporting the Discovery of New Therapies
Founded in 2002 by Warren Lammert and Orrin Devinsky MD, the Epilepsy Therapy Project merged with the Epilepsy Foundation in 2012. The vision is to foster innovation and support scientific advancements that could result in new treatments for people with epilepsy. Most importantly, we want to get new therapies to people with epilepsy faster – in a timeframe that matters.
Key Epilepsy Therapy programs include: