Chimeric Molecule for the Treatment of Depression

Application

Small molecules for treating depression and/or depression associated with cancer/chemotherapy.

Key Benefits

• Potentially a dual mechanism compound – working via monoamine reuptake inhibition and HDAC inhibition (epigenetic modification).
• Quicker acting compound compared to current therapies in the market. Works better than the most potent HDAC inhibitors that crosses blood-brain-barrier (BBB) (HDAC inhibitors are known to be effective against depression via inhibiting neuro-inflammation signaling.

Market Summary

Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behavior, feelings and sense of well-being. If depression goes un-treated or is treated inappropriately, it is potentially fatal leading to suicide. Depression is under-diagnosed in various reasons. Current state of treatment is the use of anti-depressants drugs, psychotherapy, or a combination of both. Most common anti-depressant drugs work by inhibiting serotonin and multiple monoamine neurotransmitter reuptake by presynaptic neurons but they all suffer from a delayed onset in effectiveness, meaning the drug must be taken for multiple weeks before a clinical effect is seen. In addition, the current drugs work on 2/3 of the patients and 1/3 of the initial responders develop resistance. Therefore, there is a current need for faster acting drugs with improved efficacy and safety.

Technical Summary

Emory researchers have designed a class of chimeric compounds that combine monoamine reuptake inhibition with a Histone Deacetylase (HDAC) inhibitor. HDAC inhibitors have been shown to be effective against neuroinflammation. They have been tested effective against depression in preclinical animal models and patients with brain tumors. This dual-mechanism compound may reduce the treatment time necessary before seeing an effect and improve efficacy, compared to current treatments for depression. By combining both functions into this molecule they could be used as an anti-depressant with improved efficacy over current drugs.

Developmental Stage

• Molecules have been designed and screened via molecular docking simulation against HDAC and SSRI.
• They have been tested in proof-of-concept animal models for depression.
• Their safety has been tested in vitro and found much safer than HDAC inhibitors on cell viability.