Columbia Technology Ventures

FixR: Late sodium current peptide inhibitor for treating cardiac arrhythmias

This technology, FixR, is a modified peptide and delivery system aimed at reducing pathogenic late sodium currents, which are implicated in cardiac and neurological diseases, including cardiac arrhythmia.

Unmet Need: Specific and effective late sodium current blockers

A “late” or “persistent” sodium current disrupts sodium channel inactivation in the heart and results in cardiac arrhythmias and sudden cardiac death. Current therapeutics to regulate late sodium currents include small molecules with varying efficacy and low selectivity in targeting late currents over other currents present during the cardiac cycle, which can lead to frequent negative off-target effects. Therefore, identifying improved strategies with better selectivity for late sodium current inhibition is critical for developing potential therapeutics to treat cardiac arrhythmogenic syndromes.

The Technology: Cell-specific peptide for late sodium current inhibition

This technology, called FixR, incorporates a peptide derived from the endogenous sodium channel modulator, fibroblast growth factor homologous factor (FHF), with a combined delivery system. The FHF derivative in FixR is a more potent inhibitor of late sodium currents than endogenous cardiac FHF, making it an ideal therapeutic. The delivery is conducted via adeno-associated virus (AAV) vectors and cell-penetrating peptides (CPP) for cell-specific delivery and control. While the technology is primarily aimed at cardiac disease, late sodium currents have a pathophysiological impact in neurological and pain-related diseases, creating the potential for FixR to be expanded as a therapeutic for non-cardiac diseases.

This technology has been validated in HEK293 cells, cardiomyocytes derived from patient-derived induced pluripotent stem cells (iPSCs), and myocytes from transgenic mice.

Applications:

  • Therapeutic for cardiac arrhythmias, heart failure, and long QT syndrome 3
  • Therapeutic for neurological disorders, including epilepsy, autism spectrum disorders, and pain-related diseases
  • Therapeutic for skeletal muscle conditions such as myotonia
  • Research tool to inhibit late sodium current for electrophysiology

Advantages:

  • Increased selectivity for late sodium currents compared to existing therapies
  • Reduced potential for negative side-effects
  • Highly specific delivery to target cells
  • Reliable at reducing late sodium currents in specific cells
  • Multiple methods of delivery including a cell penetrating peptide or a viral or plasmid vector

Lead Inventor:

Manu Ben-Johny, Ph.D.

Patent Information:

Patent Pending (US20250049953)

Related Publications:

Tech Ventures Reference: