Lixte Biotechnology Holdings, Inc.'s Lead Compound LB-100 Reported to Rapidly Improve Symptoms in a Rodent Model of Depression
EAST SETAUKET, NY-(Marketwired - Feb 3, 2016) - Lixte Biotechnology Holdings, Inc. (OTCQB: LIXT) announced that neuroscientists at the French Institute of Health and Medical Research (Inserm) using a mouse model of depression have identified protein phosphatase 2A (PP2A) as a potential pharmacological target for therapy. Administration of LB-100, Lixte's proprietary inhibitor of PP2A, rapidly reduced depressive-like symptoms in these conditioned animals. The findings were published in the journal Nature Medicine on January 25th, 2016.
John S. Kovach, MD, founder and president of Lixte said, "Dr. Manuel Mameli, Inserm investigator, and Dr. Salvatore Lecca in his team at Inserm Unit 839, the Institut du Fer a Moulin, have identified increased activity in a specific region of the brain in mice showing depressive symptoms after stressful experience. This hyperactivity returns to normal after a single administration of LB-100. Dr. Mameli, in a press release from Inserm (http://presse.inserm.fr/en/treating-depressive-symptoms-from-their-roots/22124/) is quoted 'Our study unravels early cellular mechanisms able to trigger complex behavioral responses. Our study further highlights the role of the lateral habenula in the aetiology of depression. Our results provide insights on a novel potential pharmacologic target that could be studied for a therapy of mood disorders.'"
Dr. Kovach continued, "We are very interested in the findings of Dr. Mameli and his team. Their observation of rapid amelioration of the depressive symptoms by LB-100 in widely used rodent models encourages us to see if these findings translate to patients with refractory depression. As Lixte recently reported, the initial clinical study of LB-100, a Phase 1 trial in cancer patients, revealed stabilization of several types of cancer without dose-limiting toxicity, with some patients receiving LB-100 for several months. We believe a proof-of-concept clinical study of LB-100 in refractory depression is warranted. Such a trial is especially attractive because, if the results of the animal studies hold true in patients, improvement in symptoms would be expected to occur in a matter of hours rather than after weeks of treatment required by most compounds available for depressive symptoms."
"It is not surprising," Dr. Kovach added, "that a 'targeted compound' such as LB-100 which has anticancer activity would potentially have activity in non-neoplastic diseases. Many cancers have acquired genetic alterations that perturb functions of the PP2A pathway while normal tissues do not. We believe the activity of LB-100 against different types of cancer in model systems results from its targeting an already genetically disturbed PP2A pathway in the cancer but not in normal cells. Mameli and colleagues have now shown that non-genetic dysregulation of PP2A activity associated with depressive-like symptoms arises in a focal region of the brain in mice exposed to acute stress, and that targeting this abnormal PP2A function with LB-100 eliminates symptoms and restores normal PP2A activity. As altered PP2A function is known to be present in other benign diseases, there are several, if not many, potential applications of PP2A modulation to be explored."
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