BrainCells Inc., a leading biotechnology company developing novel compounds for the treatment of central nervous system (CNS) diseases, has successfully completed the phase I single ascending dose (SAD) study of BCIK838 and the company has initiated the phase I multiple ascending dose (MAD) study.

The SAD study evaluated BCIK838 for safety, tolerability, pharmacokinetics and food effect in healthy male subjects. Single oral doses of BCIK838 up to 900 mg were administered and the drug was well tolerated. No serious adverse events were reported and all adverse events were mild in intensity, transient, and resolved without sequelae.

“BCIK838’s biological activity mimics that of ketamine, an intravenous anesthetic, which has been shown to be efficacious in treating patients with TRD. Since ketamine is associated with a number of unwanted side effects such as shortKterm dissociation and psychosis, safer compounds that act in a similar fashion promise to revolutionize the way the disease is managed for these patients.” said Robert Williamson, CEO.

BCIK632 increases synaptic glutamate by inhibiting the mGlu2/3 autoKreceptor, which is located predominantly at the preKsynaptic site.  As in the case of ketamine, the longKlasting efficacy of BCIK632 can be blocked by either inhibition of AMPA receptors, mTOR or the BDNF signaling pathway. In contrast to ketamine, BCIK632 does not cause psychosis or dissociative effects. In addition, BCIK632 also stimulates serotonin release and, after chronic dosing, hippocampal neurogenesis.

“BCIK838 is an oral prodrug for the active compound BCIK632 that is an mGluR2/3 antagonist” said John Hutchinson, PhD, senior vice president of Research.  “BCIK632 has been shown to work acutely in a range of animal models of depression, anxiety, cognition and Alzheimer’s disease.” “BCIK838 has the potential to provide meaningful clinical benefits for patients suffering from TRD. We believe that BCIK838 may have comparable efficacy to ketamine without the liability of psychosis, the need for intravenous administration or inpatient monitoring.  Furthermore, the neurogenic effect of BCIK838 in the hippocampus suggests that BCIK838 may be a novel treatment for a broader population of patients with mood or cognitive disorders” said Steven D Targum MD, chief medical officer. “The phase I MAD study will be completed by June and we intend to study MDD  patients who are treatmentKresistant shortly thereafter.”

Major Depressive Disorder (MDD) is a highly prevalent disorder causing  marked social and economic problems for affected patients and their families. According to the World Health Organization, MDD is the leading cause of disability worldwide. MDD is associated with high morbidity contributing to greater health risks and a high risk for mortality. Many depressed patients are not correctly diagnosed and may receive no treatment at all.  Many other MDD patients who are treated do not achieve a full remission of their symptoms despite treatment. In the NIMH sponsored STAR*D study  (Sequenced Treatment Alternatives to Relieve Depression), only 36.8 per cent of patients achieved remission with citalopram, a firstKline antidepressant treatment in the sequence. In fact, several other studies have  also shown that less than 50% of treated MDD patients achieve more than a 50 per cent reduction of their symptoms. Some MDD patients appear to be resistant to antidepressant treatment.

Treatment resistant depression (TRD) is defined as the failure to fully respond to an antidepressant treatment despite having had an adequate dose  and duration of treatment. Despite the availability of many new therapeutic  agents in recent decades, these medications have revealed issues related to limited efficacy and tolerability. Currently available antidepressants are associated with adverse events, such as gastrointestinal symptoms, agitation,  and sexual dysfunction that may affect treatment compliance.