At Damona, we combine our deep knowledge of brain cell microcircuits with precision chemistry and targeted neuropharmacology to develop small-molecule therapeutics that restore optimal brain function.

Damona’s discovery has unlocked a new approach to reverse cognitive deficits in brain disorders.
Our drug development programs are based on our discovery of a highly conserved “weak link” involving the GABA-A receptor in brain microcircuits that is dysfunctional across some of the most common brain disorders, reducing connection between brain cells and damaging information processing and cognitive functions. GABA is the main inhibitory neurotransmitter in the brain, and drugs that increase GABA function are used to treat anxiety, sleep disturbances, pain, and epilepsy—but their activity is broad and affects many subtypes of GABA-A receptors, leading to common side effects. Damona’s discovery has unlocked the rich and untapped potential of targeting specific subunits of the GABA-A receptor.

Our lead product candidate targets the α5 subunit-containing GABA-A receptor.
The α5-GABA-A receptor is uniquely located in cognition-relevant brain areas—the hippocampus and frontal cortex—where it mediates the functions of somatostatin (SST)-containing, GABA-producing cells and pyramidal neurons. Loss of key structures—dendritic spines—in pyramidal neurons that maintain neural connections is a hallmark of psychiatric and neurodegenerative brain disorders and their associated cognitive deficits. Damona discovered that the cell microcircuit formed by SST cells and α5-GABA-A receptors on pyramidal neurons is deficient in depression, Alzheimer’s disease, schizophrenia, and other CNS disorders. In preclinical models, our small molecules targeting the α5-GABA-A receptor augmented its function and rescued this deficient pathway, reversing cognitive deficits.

We envision a future where patients with brain disorders have access to the missing therapeutic elements they need to restore brain health and cognitive function—reversing memory loss, reduced brain processing speed, and challenges with executive functioning skills—so they can experience more fulfilling lives.