Ebselen, abandoned as Stroke Rx, has Successful 1st human Trial as Repurposed Bipolar disorder Rx

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double-blind, placebo-controlled trial with healthy participants, acute oral ebselen reduced brain myo-inositol in the anterior cingulate cortex, consistent with CNS target engagement. Ebselen decreased slow-wave sleep and affected emotional processing by increasing recognition of some emotions, decreasing latency time in the acoustic startle paradigm and decreasing the reinforcement of rewarding stimuli. In summary, ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder, which can be tested in future clinical trials.

Ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder, which can be tested in future clinical trials.

A drug destined for the scrap heap has been rescued by Oxford scientists. They used a database of ‘failed’ drugs, found to be safe but ineffective for their proposed use, to identify ebselen as a possible alternative to lithium, the main treatment for people who are bipolar.

Ebselen was under development as a treatment for stroke, but was abandoned by its manufacturer in the final phase of clinical trials. However, those trials proved that the drug was safe for use in humans. Initial tests of ebselen as a treatment for bipolar disorder were carried out in mice. That research, reported in early 2014, found that results were promising, so the researchers were able to use the existing safety information to fast track an initial trial of ebselen in people.

Dr Grant Churchill explained: ‘Lithium has been used for over 60 years and remains the most effective treatment for bipolar disorder, but suffers from toxicity and has many side effects. It is toxic at only twice the right dose and can cause weight gain and thirst. Long-term lithium use can lead to kidney damage. The side effects also encourage people to stop taking it, which means they can relapse.

METHOD: In a small trial, healthy adult volunteers were given a course of ebselen. They carried out a number of tests of brain function, provided blood samples and also went through an MRI scan.
RESULTS: showed that ebselen had similar effects on the brain to lithium. The next stage will be a full clinical trial to test the effectiveness of ebselen as a treatment. The researchers have obtained funding from the Stanley Medical Research Institute in the United States to conduct a ‘proof of concept’ study for ebselen in patients with bipolar disorder. It is hoped that the study will start in later in 2016

Should these successes continue, ebselen will be one of only a few examples of a ‘rescued drug’, where a new use has been found for a failed drug compound. Dr Sridhar Vasudevan said: ‘By rescuing a drug, we benefit from the earlier research and the work of the earlier researchers has a new value. Rather than remaining unused on the shelf of a pharmaceutical company or academic laboratory, drug compounds become available for other uses.
http://www.eurekalert.org/pub_releases/2015-12/uoo-hts120815.php