Research Team co-led by Dr Geoffrey Lau discovers a new drug candidate for epilepsy treatment

Dr Geoffrey Lau Chun-Yue (left) with his research team members Dr Guo Anni (centre) and Mr Li Huanhuan.

A research team co-led by Dr Geoffrey C. Y. Lau, Assistant Professor at the Department of Neuroscience, City University of Hong Kong (CityU), has recently identified and developed a new drug for treating temporal lobe epilepsy (TLE).

TLE is one of the most common types of epilepsy worldwide. Although patients can be treated by existing medications, many of them remain unresponsive to drug treatment. Hence, new medications and drug targets are needed. Connexin-based gap junctions and hemichannels in brain glial cells are implicated in TLE, but blocking gap junctions can lead to undesirable side effects.

Dr Lau’s research group identified a new small-organic molecule called D4, which selectively blocks connexin hemichannels (but not gap junctions). They investigated its effect in treating TLE using a mouse model. Dr Lau’s team found that D4 strongly suppresses the TLE-induced neuroinflammation, curbs TLE seizures, and increases animal survival rate.

D4 treatment decreases proliferation and activation of astrocytes in two different brain regions. Pilocarpine was injection into mice intraperitoneally to induce seizures. Seven days after pilocarpine-induced seizures, we observed a chronic elevation of the number of astrocytes. Pre-pilocarpine or post-pilocarpine, single injection of the new hemichannel antagonist D4 significantly curbs the proliferation of astrocytes, thus reducing neuroinflammation. APC, anterior piriform cortex; CA1, cornu ammonis area 1 of the hippocampus; DG, dentate gyrus area of the hippocampus; GFAP, glial fibrillary acidic protein (marker of astrocytes); DAPI, marker of cell nuclei; L1, L2, L3, layers 1, 2 and 3 of APC; s.o., Stratum oriens; s.p., Stratum pyramidale; s.r., Stratum radiatum; m.l., molecular layer; d.g.l., dentate granule cell layer; h, hilus.

This research is the product of a collaboration between the corresponding authors, Dr Geoffrey Lau (CityU Neuroscience) and Dr Juan C Saez (University of Valparaíso, Chile). The findings entitled, “Inhibition of connexin hemichannels alleviates neuroinflammation and hyperexcitability in temporal lobe epilepsy”, is published at a leading international journal, Proceedings of the National Academy of Sciences of the United States of America (PNAS) (https://www.pnas.org/doi/10.1073/pnas.2213162119).

The first author is Dr Anni GUO, a postdoc in Dr Lau’s lab who graduated and obtained her PhD from CityU’s Interdisciplinary PhD Programme in Veterinary Medicine in collaboration with Cornell University. Funding on the CityU side is provided by the Hong Kong Research Grants Council (ECS 21103818, GRF 11104320 and GRF 11104521 to C.G.L.), Shenzhen General Basic Research Program (JCYJ20190808182203591 to C.G.L.), a grant from ITF-InnoHK, and internal funds from City University of Hong Kong (to C.G.L.).

News Coverages

Research Team co-led by Dr Geoffrey Lau discovers a new drug candidate for epilepsy treatment

News Coverages

CityU Research Stories

城大研究

香港城大研創

Nature Reviews Neurology

逻辑神经科学 (Logical Thinking Neuroscience)

EurekAlert!