The Clearance-Signaling Gap

The pathology is framed as dysregulated signaling kinetics, not simple neurotransmitter deficit. Our program targets the velocity of signal termination.

Synaptic residence time is often manipulated broadly, creating dissociation between neurotransmitter presence and information quality.

Suppression Agents (alpha-2 agonists)

Global attenuation of noradrenergic tone can reduce hyperarousal while simultaneously dampening salience, initiation, and motivation. The clinical tradeoff is calm with functional flattening.

Occlusion Agents (reuptake inhibitors)

Transporter blockade can elevate extracellular exposure but may compress signaling contrast over time, with reduced separation between baseline noise and task-relevant bursts.

Polypharmacy Burden

Stacked regimens can become kinetically fragile and adherence-heavy, requiring high executive load precisely in populations where initiation bandwidth is already constrained.

The Kinetic Third Way

The Old Way Stimulants / NRIs Brute-force blockade of clearance pathways.
The Current Way Alpha-2 Agonists Brute-force suppression of upstream signaling drive.
Our Approach NET PAM Program Catalytic acceleration via allosteric modulation.

Acceleration, Not Suppression.

The objective is to increase transporter catalytic throughput (kcat) so existing clearance infrastructure resolves tonic accumulation more efficiently.

This is a kinetic strategy: not adding more neurotransmitter, not shutting signaling down, but improving turn-over dynamics of endogenous processing. Conceptually: adjust the drain rate, not the faucet pressure.

Spatiotemporal Constriction

A three-part mechanism hypothesis for tighter, higher-fidelity signaling.

Accelerate Clearance Velocity.

Increase NET turnover efficiency to reduce tonic dwell-time of extracellular norepinephrine and tighten baseline clearance kinetics.

Preserve Phasic Fidelity.

Prioritize restoration of baseline-to-burst contrast so task-relevant phasic events remain distinguishable over tonic background activity.

Support Receptor Competence.

Lowering prolonged extracellular load is expected to improve downstream signaling responsiveness through less persistent receptor stress exposure.

Therapeutic Focus

Initial target populations where kinetic mismatch is a primary treatment barrier.

Treatment-Resistant Hyperarousal

Patients showing paradoxical outcomes under conventional suppression or blockade approaches, with persistent tonic bias and poor functional recovery.

Executive Dysfunction

Profiles where cognitive capacity is present but initiation remains impaired, and the dominant disability is conversion of intent into action.

Kinetic Phenotypes

Responder groups enriched for transport inefficiency signatures where allosteric acceleration may improve signal timing and behavioral output.

See how this translates into development milestones.

View Mission