![\"\"](\"http:\/\/sites.unica.it\/pe2026\/files\/2026\/05\/Ruben_Tack.jpg\")
<\/figure>OC18 – Ruben Tack<\/strong><\/p>\n\n\n\n Laboratory of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Belgium<\/p>\n\n\n\n e-mail<\/a> – LinkedIn<\/a><\/strong><\/p>\n<\/div><\/div>\n\n\n\n <\/p>\n","protected":false},"excerpt":{"rendered":" OC18 – Ruben Tack Laboratory of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Belgium e-mail – LinkedIn Towards Closed-Loop Spatiotemporal Treatment of Drug-Resistant Epilepsy With Photopharmacology Tack Ruben1, Vergaelen Marijke2, Guerrero Ancil Javier\u00b2, Raedt Robrecht2 […]<\/p>\n","protected":false},"author":9643,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1756","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1756","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/9643"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=1756"}],"version-history":[{"count":2,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1756\/revisions"}],"predecessor-version":[{"id":1802,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1756\/revisions\/1802"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=1756"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=1756"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=1756"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Towards Closed-Loop Spatiotemporal Treatment of Drug-Resistant Epilepsy With Photopharmacology<\/strong><\/strong><\/td><\/tr> Tack Ruben1<\/sup>, Vergaelen Marijke2<\/sup>, Guerrero Ancil Javier\u00b2, Raedt Robrecht2<\/sup> and Van Calenbergh Serge1<\/sup>
<\/em>
1<\/sup><\/em> Laboratory of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Belgium;
2<\/sup><\/em> 4Brain, Faculty of Medicine & Health Sciences, Ghent University, Belgium;<\/td><\/tr>Abstract<\/strong>
Photopharmacology holds significant promise for the treatment of neurological diseases such as epilepsy, a condition affecting approximately 50 million people worldwide, of whom nearly 30% suffer from a drug-resistant form. Activation of the adenosine A1 receptor (A1R) is well established as a mechanism for suppressing neuronal excitability and seizure activity. However, systemic administration of A1R agonists, including N6-cyclopentyladenosine (CPA), has failed clinically due to unacceptable peripheral side effects arising from the ubiquitous expression of A1Rs throughout the body. To overcome these limitations, a photocaged derivative of CPA (cCPA) was designed using 7-diethylamino-4-hydroxymethylcoumarin (7-DEACM) as a photolabile protecting group. This strategy enables light-triggered release of the A1R agonist, allowing on-demand, spatially confined activation of A1R in seizure-relevant brain regions such as the hippocampus. The feasibility of delivering CPA in a closed-loop controlled manner has been demonstrated in both ex and in vivo settings, with the latter employing intracerebroventricular administration of cCPA [1]. While these results are encouraging, the 7-DEACM photoprotecting group carries notable limitations. Its photorelease requires near-UV light (405 nm), which penetrates biological tissue poorly and carries a risk of cytotoxicity. Furthermore, 7-DEACM exhibits limited aqueous solubility, constraining its applicability in physiological settings. To address these shortcomings, the uncaging wavelength of the coumarin was red-shifted towards a more biocompatible range and aqueous solubility was improved by introducing distinct hydrophilic side chains at the 7-position of the coumarin core. Additionally, incorporation of a methyl group at the 4-position was pursued to improve uncaging kinetics, thereby further mitigating the risk of phototoxicity in the brain. Figure 1 illustrates the aforementioned structural optimizations incorporated into the coumarin photocage. The resulting caged anti-epileptics were systematically characterized for their aqueous solubility and uncaging kinetics. Following confirmation of efficient photorelease, their anticonvulsant potential was evaluated in acute hippocampal brain slices prepared from an intrahippocampal kainic acid induced mouse model of temporal lobe epilepsy, using multielectrode array recordings to assess seizure suppression upon light-triggered agonist release [2]. Together, these improvements represent a meaningful step towards a clinically viable photopharmacological strategy for the on-demand, spatiotemporally controlled treatment of drug-resistant temporal lobe epilepsy.
![\"\"](\"http:\/\/sites.unica.it\/pe2026\/files\/2026\/05\/Figure_1_Tack_Ruben_Abstract.jpg\")
Figure 1. <\/strong>Optimized coumarin scaffold highlighting key structural modifications to improve photopharmacological properties.<\/td><\/tr>References <\/strong>
[1] Spanoghe J, Wynendaele E, Vergaelen M, De Colvenaer M, Mariman T, Vonck K, e.a. Photopharmacological activation of adenosine A1 receptor signaling suppresses seizures in a mouse model for temporal lobe epilepsy. J Controlled Release. 2025;381:113626. doi:10.1016\/j.jconrel.2025.113626
[2] Craey E, Vergaelen M, Van Calenbergh S, Spanoghe J, Carrette E, Vonck K, e.a. Feedback control of excitability and high K+ induced epileptiform bursts in male rat hippocampal slices with a photocaged adenosine A1 receptor agonist. Br J Pharmacol. 2026 doi:10.1111\/bph.70349<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n