Sage Therapeutics

therapeutic approach

Our Approach

Allosteric Modulation of GABA and NMDA

SAGE’s proprietary Positive and Negative Allosteric Modulator (PANAM) chemistry platform focuses on two key, validated nervous system targets: GABAA and NMDA receptors, the primary inhibitory and excitatory receptors that mediate “fast” synaptic transmission in the brain. These targets are critically important and are now better understood than ever before due to decades of biological research, recent scientific progress and SAGE’s own pioneering work.

Allosteric modulation is a way of influencing the levels of neurotransmitters without acting directly as an agonist or antagonist at the receptor.  SAGE’s data suggest this approach may avoid intrinsic compensatory mechanisms that hamper the activity and safety of many currently available medications.

Correcting imbalances of GABAA and NMDA activity through allosteric modulation offers significant opportunity to treat many diseases.  The ability to up-regulate and down-regulate GABAA and NMDA with high selectivity may minimize off-target effects.  

SAGE’s proprietary PANAM platform is a powerful chemistry engine driving development of highly selective and potent positive and negative allosteric modulators of GABAA or NMDA receptors to improve risk-benefit and reduce off-target toxicities seen with traditional therapies.  Importantly, SAGE’s medicines are modeled after endogenous molecules (naturally occurring), thereby increasing the likelihood that our medicines will be active at relevant CNS sites.