Research & Development
Our Platform for Region-Selective Drug Screening
Receptors don't act alone. Receptor-associated scaffolding proteins form complexes with receptors to support their function. They are expressed in discrete brain regions. A prime example: transmembrane AMPA receptor regulatory proteins (TARPs), which co-localize with glutamate receptors. We leverage TARPs within our platform—cell-based screening assays expressing our proteins of interest— to discover region-specific compounds and to explore unique binding sites.
Our Focus: Ionotropic
Glutamate Receptors
Ionotropic glutamate receptors, like AMPA receptors, play a key role in the brain’s excitatory signaling. Their dysfunction, even in one brain area, underlies many disorders.
Glutamate receptor drugs do exist, but their broad activity causes unwanted effects. We use TARPs to direct medicines to disease-driving regions while sparing others, limiting side-effects and increasing efficacy.
Pipeline
Programs
AMPA receptor/ TARPγ4 Program
NL-101 series for PTSD
NL is developing a negative allosteric modulator (NAM) for amygdala-specific AMPA receptors. It achieves regional specificity hrough its selective targeting of TARPγ4, which co-localizes with AMPA receptors at the synapse. AMPA receptors are distributed throughout the brain; however, TARPγ4 is most expressed in the amygdala, the brain's fear center and an important region for PTSD symptom development. NL’s lead asset is currently in lead optimization and preclinical studies.
PTSD Imaging Tracer
NL is using the AMPA receptor/ TARPγ4 platform to identify additional compounds to be developed into imaging tracers (i.e., compounds with high/ optimal target specificity and binding). Use of region-specific radiotracers will decrease diagnostic artifacts and noise. NL has previously developed a novel class of compounds that may be radiolabeled, which includes the company’s patented 18F-NVL-1 radiotracer. High levels in the amygdala would indicate PTSD.
AMPA receptor/ TARPγ8 Program
mTBI/ microTBI tools
NL is in the Discovery phase with its AMPA receptor/ TARPγ8 platform to identify additional compounds to be developed into imaging tracers (i.e., compounds with high/ optimal target specificity and binding). TARPγ8 is expressed in the temporal lobe and hippocampus, a common focal point of traumatic brain injuries. Resulting compounds from this screen may be used as both a region-specific therapeutic or diagnostic imaging tracer to detect microTBI at the site of injury for the earliest possible intervention.
Future indications and uses of this platform include therapeutic and diagnostic tools for epilepsy and Alzheimer’s Disease.