Strategies for boosting local adenosine A1 signaling as a treatment for focal epilepsy: from positive allosteric modulators of the inhibitory A1 receptor to deep brain stimulation and photopharmacology.

01 January 2019 → Ongoing
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Neurological and neuromuscular diseases
    • Neurophysiology
Deep brain stimulation Photopharmacology Epilepsy
Project description

Epilepsy is a common neurological disorder, characterized by spontaneous recurrent epileptic seizures. Despite adequate treatment with anti-epileptic drugs, still 30% of the patients continue to have seizures or suffer from severe medication-related side effects due to the large doses of AED they need to take. Therefore, innovative treatments for epilepsy are highly needed. The neuromodulator adenosine, which interacts with A1 receptors (A1Rs), has been shown to exert a seizure-suppressing effect. Strategies aiming at increasing adenosine levels and thus enhancing A1R signaling, may be a promising approach in the treatment of epilepsy. In this project, we will investigate the seizure-suppressing effect of T62, a positive allosteric A1R modulator that enhances the effect of adenosine and A1R signaling. Next, the potential of T62 to enhance the efficacy of deep brain stimulation (DBS), an FDA-approved treatment for epilepsy, by means of enhancing A1R signaling will be evaluated. Eventually, photopharmacology, a fast emerging approach in which light-sensitive drugs such as caged T62 can only be activated upon local illumination of a specific wavelength, will be studied. Using this methodology, we aim to demonstrate that photopharmacology in combination with T62 and DBS is a viable strategy for precision treatment for drug-resistant epilepsy patients.