Application

Family of small molecule 7,8-dihydroxyflavones that act as TrkB agonists, including a prodrug, for treating a number of neurological conditions and diseases.

Key Benefits

• Has antidepressant-like properties, improves cognitive function, and promotes neuronal survival in animal models of neurological diseases.
• Whereas current anti-depressant and anti-anxiety medications take 1-2 months to take effect, and frequently produce very harsh side effects, 7,8-dihydroxyflavone is a potent anti-depressant that demonstrates therapeutic efficacy within a few days.
• Substantial patent portfolio with large number of protected derivatives.
• May be effective against several neurological disease indications.

Market Summary

Brain-derived neurotrophic factor (BDNF), a ligand that activates the TrkB receptor, is of interest as a therapeutic target due to its neuroprotective properties. Treatment with BDNF, however, is not an option due to poor efficiency, bioavailability, adverse side effects, and inability to cross the blood brain barrier. Because dysregulation of BDNF and TrkB receptor activation is implicated in a variety of neurological diseases, the impact of a TrkB agonist could prove to be quite profound. Some disorders that may benefit from this therapeutic include Parkinson’s disease, Alzheimer’s disease, stroke, Rett Syndrome, Huntington’s disease, Amyolateral Sclerosis, glaucoma, macular degeneration, anxiety, and depression.

Technical Summary

Researchers at Emory have identified a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), that has improved activity, bioavailability, and fewer deleterious side effects. Moreover, Dr. Ye and colleagues are doing further structure activity relationships assays to identify additional modifications that could further improve upon this small molecule therapeutic. Treatment with 7,8-DHF improves Parkinsonian symptoms in animal models, reduces anxiety, increases synaptic plasticity, and promotes neuronal survival. Through a structure-activity relationship study, a derivative of 7,8-DHF was found to have higher and more prolonged TrkB agonistic activity than 7,8-DHF in vitro. There is currently a lead compound which has anti-apoptotic activity.

Developmental Stage

This small molecule program has a lead candidate and additional work is ongoing.