CERC-611

A potent and selective transmembrane AMPA receptor regulatory proteins ("TARP")-γ8-dependent AMPA receptor antagonist

CERC-611

Targeting Partial-Onset Seizures in Epilepsy

CERC-611 is being developed as an adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy.

What are AMPA receptors?

AMPA receptors are glutamate-sensitive ion channels on postsynaptic membranes of excitatory synapses in the central nervous system and are largely responsible for mediating fast neurotransmission across synaptic gaps. AMPA receptor antagonists are known anticonvulsant agents and their ability to down-modulate excitatory neurotransmission is key to their antiepileptic therapeutic potential.

The role TARPs play with AMPA receptors

Transmembrane AMPA receptor regulatory proteins (TARPs) are a recently discovered family of proteins that have been found to associate with and modulate the activity of AMPA receptors. Several TARPs are fairly region-specific in the brain, leading to physiological differentiation of AMPA receptor activity. For example, TARPγ2 (stargazing)-dependent AMPA receptors are primarily localized in the cerebellum and cerebral cortex and TARPγ8-dependent AMPA receptors are localized primarily in the hippocampus, a region which is particularly relevant to seizure origination and/or propagation. It has been theorized that targeting individual TARPs may enable selective modulation of specific brain circuits without globally affecting synaptic transmission.

Attributes
of CERC-611

  • First molecule to selectively target TARP-γ8-containing AMPA receptors
  • Effective in wide range of animal models of epilepsy
  • Oral formulation

About the Disease

Epilepsy is a neurological disorder affecting over 50 million people worldwide (World Health Organization Data)

According to the CDC, in 2015 about 3 million U.S. adults and 470,000 children had active epilepsy (under treatment or with recent seizures). The number of adults with active epilepsy rose from 2.3 million in 2010 to 3 million in 2015. The number of children with the condition increased from 450,000 in 2007 to 470,000 in 2015. These increases are likely due to population growth.

Mechanism of Action

Selectively target and functionally block regionally-specific AMPA receptors

CERC-611 is the first molecule to selectively target and functionally block regionally-specific AMPA receptors after oral dosing. This selectivity was engineered into CERC-611 using structure-activity relationship information to achieve selective blockade of the AMPA receptor regulatory protein or TARP-γ8 while sparing AMPA receptors associated with TARP γ2. CERC-611 is the first molecule to selectively target TARP-γ8-containing AMPA receptors.