Chimeric protein for directly modulating calcium ion channel activity

This technology, called Genetically Encoded Enhancer of Ca2+ Currents (GEECC), is a genetically encoded enhancer of calcium currents to directly modulate calcium currents in L-type Ca2+ channels.

Unmet Need: Engineered chimeric proteins for ameliorating calcium ion channel dysfunction

Current methods to treat cardiovascular disease and neurological disorders resulting from calcium ion channel dysfunction rely largely on calcium or potassium ion channel blockers. However, many antiarrhythmic medications remain unreliable treatments, as they demonstrate off-target effects, and, paradoxically, may increase the risk of arrhythmias. Moreover, this course of treatment fails to directly resolve calcium ion channel dysfunction at its source. Patients with more severe forms of arrythmia may resort to surgical implantation of defibrillator devices, which poses its own set of risks. Currently, there remains a lack of reliable treatment options for patients with dysfunctional calcium ion channels.

The Technology: Activation of L-type calcium channels with chimeric proteins

This technology is a genetically encoded chimeric protein to rescue dysfunctional action potentials in L-type calcium channels in specific tissues. This chimeric protein consists of a functional domain of a subunit found in calcium ion channels known to directly influence calcium currents in heart cells and a nanobody. When this protein is administered to either cardiac or neural cells, calcium channel activity is rescued.

This technology has been validated with iPSC-derived neurons and rat neurons.

Applications:

• Treatment for cardiac arrhythmia, dilated cardiomyopathy, short QT syndrome, Brugada syndrome and Rett syndrome
• Research tool for studying rhythmic effects of calcium flux
• Disease progression modeling
• Research tool to study the function of calcium in neural pathways

Advantages:

• Tissue-specific targeting of L-type calcium channels
• Minimal adverse effects in off target tissues
• Applicable to a wide array of calcium ion channel dysfunction disorders
• Targeted treatment at source of disease

Lead Inventor:

Manu Ben-Johny, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Del Rivero Morfin PJ, Chavez DS, Jayaraman S, Yang L, Kochiss AL, Colecraft HM, Liu XS, Marx SO, Rajadhyaksha AM, Ben-Johny M. “A Genetically Encoded Actuator Selectively Boosts L-type Calcium Channels in Diverse Physiological Settings.” bioRxiv [Preprint]. 2023 Sep

• Del Rivero Morfin PJ, Chavez DS, Jayaraman S, Yang L, Kochiss AL, Colecraft HM, Marx SO, Ben-Johny M. “Abstract P3142: Engineering A Genetically Encoded Enhancer Of L-type Ca2+ Currents.” Circulation Research. 2023 Oct 13;133

Tech Ventures Reference:

• IR CU23388

• Licensing Contact: Kristin Neuman