PROBLEM

Dysregulation of the cardiac ryanodine receptor (RyR2) leads to abnormal Ca²⁺ release, a central driver of serious cardiovascular diseases including congestive heart failure (CHF), catecholaminergic polymorphic ventricular tachycardia (CPVT), arrhythmogenic right ventricular dysplasia (ARVD2), and related disorders collectively known as cardiac ryanopathies. Current therapeutic strategies primarily target RyR2 indirectly and non-specifically, resulting in limited efficacy and off-target effects. FDA-approved therapies, including dantrolene and mavacamten, are associated with significant safety concerns due to their lack of specificity. There is a critical unmet need for targeted therapies that directly modulate RyR2 dysfunction with high precision and improved safety profiles.

SOLUTION

Researchers at OSU, led by Dr. Harpreet Singh, have developed a novel class of CLIC-derived peptides that directly bind to the RyR2 receptor to correct pathological Ca²⁺ leak. These engineered peptides are highly specific to RyR2 and restore normal calcium handling by stabilizing the receptor and modulating its activity. This therapeutic can be delivered as peptides or via AAV9 to enable targeted intervention at the source of dysfunction. Unlike the existing therapeutics, this first-in-class peptide-based strategy provides extremely precise modulation of RyR2 function with improved efficacy and reduced off-target effects to correct the molecular drivers of cardiac ryanopathies.

APPLICATIONS

• Treatment of cardiac ryanopathies including CHF, CPVT, ARVD2, Ca²⁺ release deficiency syndrome
• Precision therapy for patients with RYR2 gene mutations
• Gene therapy using AAV9-mediated delivery
• Platform for development of ion channel-targeting peptide therapeutics

ADVANTAGES

• High specificity: selective and high affinity binding directly to RyR2 to directly correct the underlying Ca2+ leak rather than downstream symptoms
• Enhanced safety profile: reduced off-target effects and systemic toxicity compared to current therapies
• Versatile delivery: peptide administration and compatible with AAV vectors

Seeking opportunities for out-licensing, co-development, and collaboration