Avidin presented poster titled “Q134R, a clinical candidate against Alzheimer’s disease with multiple mechanisms of action is a selective GABAA receptor antagonists with cognition improving efficacy “ in collaboration with the Brain Research Institute, University of California, Los Angeles and the Sanders-Brown Center on Aging, University of Kentucky at the AD/PDTM 2019 meeting, the 14th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders.
Authors: Orsolya Huzián, Lajos István Nagy, Levente Knapp, Gábor Molnár, István Mody, Christopher M. Norris, Gábor Tamás and László G. Puskás
Q134R exerts strong cytoprotective action and has impressive memory enhancing activity in AD and amnesia in vivo models. Q134R exhibits anti-inflammatory and NFAT inhibitory properties without suppressing direct calcineurin activation. In present study whole-cell patch clamp recordings showed after baseline recording, that Q134R (100 nM) increased the holding current significantly, reducing the cell membrane’s potassium currents. In the presence of CsCl the holding current decreased significantly.
These holding potential changes achieved by inhibiting the specific GABAA receptor. Q134R had impressive memory enhancing activity in amnesia model (scopolamine impairs short-term memory), it reversed scopolamine induced impairment of working memory in the Y-maze test in wild type, but was ineffective in the δ-GABAAR KO mice.
Given this profile, Q134R may improve cognitive function in neurodegenerative disorders, including Alzheimer’s disease.