Uncaging the potential of photopharmacology for the treatment of epilepsy

01 January 2024 → 31 December 2027
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Neurological and neuromuscular diseases
    • Medicinal chemistry
  • Engineering and technology
    • Microfabrication and manufacturing
    • Biophotonics
photopharmacology epilepsy flexible brain probes
Project description

Various brain disorders, such as epilepsy, are caused by sporadic abnormal activity of neurons in specific parts of the brain. These disorders are treated with drugs that influence the whole brain and body and therefore cause off-target side effects. Ideally drugs would act only WHEN and WHERE needed. This is possible with photopharmacology, where inactive prodrugs are activated by light. This project aims to develop original photocages, which can be linked to powerful antiepileptic drugs, thereby abolishing their pharmacodynamic activity. Such caged antiepileptic agents can be ingested and activated in the brain area of interest by locally administering light. The photocages will be designed in such a way that, after coupling to selected drugs, they produce compound that is sufficiently soluble and release upon illumination with light frequencies that penetrate deep in the brain. To activate the drugs, we will make ultra-soft probes that can be implanted without notably damaging the brain tissue and allow to measure brain activity and, when the local tissue exceeds an excitability threshold, illuminate this brain tissue to release enough of the antiepileptic drug to prevent the epileptic seizures. We aim to prove this concept in a preclinical model for temporal lobe epilepsy, the most common and most difficult to treat form of epilepsy.