Selective peptide inhibitor of late sodium current for precision arrhythmia treatment

This technology is a de novo-designed peptide modulator that selectively inhibits late sodium current in cardiac sodium channels to treat arrhythmias and heart failure without affecting normal channel function.

Unmet Need: Inhibition of pathogenic late sodium current without off-target effects.

Increased late sodium current is a driver of cardiac conditions like Long QT Syndrome Type 3 (LQT3) and heart failure, but existing drugs often lack specificity and have significant side effects. Current treatments for cardiac arrhythmias often rely on small-molecule inhibitors that block both peak and late sodium currents, which can lead to off-target effects and conduction disturbances. There is a critical need for a therapeutic agent that can precisely target the pathogenic late current without disrupting the peak current required for normal cardiac excitability.

The Technology: Selective peptide inhibitor for pathological sodium channels

This technology introduces "ELIXIR" (Engineered Late-current Inhibitor by Inactivation-gate Release), a computationally designed peptide that selectively inhibits the late sodium current of the cardiac voltage-gated sodium channel, Nav1.5. ELIXIR binds to the channel's C-terminal domain to stabilize the closed state, mechanically enhance the native inactivation process. Unlike traditional blockers, this approach allows the peptide to preferentially inhibit pathological channels while preserving the activity of normally functioning channels, which are essential for the cardiac action potential.

This technology has been validated in patient-derived iPSC-cardiomyocytes and transgenic mouse models.

Applications:

• Therapeutic for cardiac arrhythmias
• Therapeutic intervention for heart failure
• Treatment for neurological and skeletomuscular disorders (epilepsy, myotonia, etc.)
• Research tool for studying sodium channel inactivation mechanisms
• High-throughput screening platform for small molecule sodium current inhibitors

Advantages:

• High selectivity for pathogenic late current
• Targets the regulatory domain of the channel rather than the pore, avoiding blockage
• Maintains normal sodium current
• Broad efficacy across disease mechanisms
• Reduced side effects

Lead Inventor:

Manu Ben-Johny, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Mahling R, Hegyi B, Cullen ER, et al. “De novo design of a peptide modulator to reverse sodium channel dysfunction linked to cardiac arrhythmias and epilepsy.” Cell. 2025;188(22):6170-6185.e19

• Chakouri N, Rivas S, Roybal D, et al. “Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current.” Nat Cardiovasc Res. 2022;1(5):1-13

Tech Ventures Reference:

• IR CU24196

• Licensing Contact: Kristin Neuman