Translational investigation of a lithium mimetic on emotional and cognitive processing in healthy volunteers

Lead Research Organisation: University of Oxford
Department Name: Pharmacology

Abstract

Bipolar disorder disease is a chronic illness characterized by recurrent episodes of aberrant mood that affects around 3% of the world's population. Current therapies for bipolar disorder such as lithium, valproic acid and atypical antipsychotics, such as seroquel, cause serious side effects including liver and kidney damage. There is therefore an urgent need for new therapies that allow long-term mood stabilisation in patients, but are more favourably tolerable. In this project, we propose to confirm the suitability of a known antioxidant that has proven to be safe in humans as a lithium replacement candidate. Our drug inhibits the enzyme inositol monophosphatase, a candidate therapeutic target of lithium and also alters mood and behaviour in animals in a manner similar to lithium. This drug, if successful therefore, would offer for the first time, the potential for physicians to treat bipolar patients without exposing them to harmful side effects.

Publications

10 25 50
publication icon
Singh N (2013) A safe lithium mimetic for bipolar disorder. in Nature communications

publication icon
Singh N (2016) Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans. in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

publication icon
Masaki C (2016) Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing. in Psychopharmacology

publication icon
Masaki C (2016) Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla. in Psychopharmacology

 
Description The IP was sold through OUI, Oxford's tech transfer office, to an American Biotech (Sound Pharmaceuticals) for £600 k who have committed to developing ebsleen for bipolar disorder. Should ebselen ultimately be approved and marketed, the University and the inventors will get a royalty stream. It is a shame that the infrastructure and will was/is not in place so that the drug could have been taken forward in the UK.
First Year Of Impact 2016
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic
 
Title TREATMENT OF BIPOLAR DISORDER 
Description The invention relates to sulphur- and/or selenium-containing compounds that can inhibit the enzyme inositol monophosphatase (IMPase), and which can be used in treating conditions that are treatable through inhibition of this enzyme, such as bipolar disorder, the compounds having a structure of Formula I, or is a pharmaceutically acceptable salt thereof; Formula I; in which: E is S or Se and each of phenyl rings A and B is optionally substituted with one or more substituents, in which each substituent is selected independently from: (1) a halogen, which is preferably selected from F, Cl and Br; (2) C1-C4 alkyl, such as C1-C2 alkyl or C1 alkyl, optionally substituted with one or more halogen atoms, each of which is preferably selected from F, Cl and Br; and (3) C1-C4 alkoxy, such as C1-C2 alkoxy or C1 alkoxy; optionally substituted with one or more halogen atoms, each of which is preferably selected from F, Cl and Br. 
IP Reference WO2012107735 
Protection Patent / Patent application
Year Protection Granted 2012
Licensed Yes
Impact It has fostered collaborative research on the drug ebselen. Funding (£1.4 M) from the MRC was secured for a study of impulsiveness in both a rat model and this will be translated into humans in an experimental medicine study. Funding from a Bipolar and Schizophrenia charity in the US called The Stanley Foundation has awarded ~£800,000 to fund a Phase 2, investigator-led efficacy trial for ebselen in bipolar disorder in Oxford. An American biotech company, Sound Pharmaceuticals, took a 3-year option, and has now (2022 December) has licensed the patent for £600k).