ARMGO Pharma, Inc., a biopharmaceutical company developing innovative small molecule drugs known as "Rycals™," which act on the ryanodine receptor calcium-release channel (RyR), announced that a study published today in the prestigious scientific journal Cell reveals the underlying role of calcium leak through the RyR as an important contributor to stress-induced cognitive dysfunction. In the published study titled "Role of Leaky Neuronal Ryanodine Receptors in Stress-Induced Cognitive Dysfunction," mice were given an orally available, brain-penetrant Rycal, known as S107, prior to and during a chronic stress protocol. The results of behavioral tests demonstrated that stressed mice have cognitive dysfunction manifested as impaired learning and memory, increased anxiety and reduced spontaneous exploratory activity as compared to untreated control mice. Mice treated with S107 showed significant improvement in all tested measures, including learning and memory, essentially becoming indistinguishable from normal unstressed mice. In addition, direct electrophysiological assessment of the hippocampus showed that stressed mice had impaired neuronal signaling measured by reduced long-term potentiation (LTP), which was significantly improved after treatment with S107. This promising and innovative research was conducted in the laboratory of ARMGO Pharma's founding scientist, Dr. Andrew Marks, Chair and Professor of Physiology and Cellular Biophysics at Columbia University College of Physicians and Surgeons.
The data generated by Dr. Marks demonstrate that orally available and brain-penetrant Rycals drugs may have therapeutic utility for the treatment of stress-induced cognitive dysfunction and a potentially broad variety of learning and memory disorders. There is a well-established link between impaired learning and mental stress, and long-term chronic stress is a major contributor to the development of neuropsychiatric, cardiovascular and autoimmune diseases, as well as to cancer. However, there is currently no effective therapy for common disorders characterized by stress-induced cognitive dysfunction, including post-traumatic stress disorder (PTSD).