Cell-based model for early-onset restrictive cardiomyopathy (RCM)

This technology is a pluripotent stem cell derived cardiomyocyte model of early-onset restrictive cardiomyopathy (RCM) based on a mutation in Filamin C (FLNC) which can be harnessed to recapitulate RCM phenotypes and to screen and identify therapeutic compounds for RCM.

Unmet Need: Recapitulating clinical phenotypes of cardiomyopathies

There is currently no cure for restrictive cardiomyopathy (RCM), a heart condition which causes stiffening of the ventricles. Treatment options for RCM are limited and although associated genetic mutations have been identified, there are no experimental models that recapitulate disease phenotypes. The identification and characterization of additional genetic mutations can aid in the development of cell lines and potentially animal models to further study RCM development and prevention. Furthermore, identifying causative mutations and underlying pathways can assist in the development of targeted drug therapies to treat RCM and the associated conditions of cardiomyopathies.

The Technology: Platform and model for studying cardiomyopathies and developing gene therapies

This technology identifies a mutation in Filamin C underlying RCM which was used to generate induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) from patients with the mutation. The technology provides a human heart tissue model and platform which recapitulates RCM in 2D and 3D cell cultures as well as the associated clinical phenotypes such as slower relaxation and prolonged calcium decay. In doing so, the technology provides a means for high-throughput screening of drug compounds that impact calcium decay as well as alternative therapeutic compounds and targets for RCM treatment.

This technology has been validated using patient-derived iPSCs used to engineer 3D cardiac tissues.

Applications:

• Disease model for restrictive cardiomyopathy (RCM)
• Platform for high-throughput drug screening for cardiomyopathies
• Platform for studying calcium decay in context of cardiomyopathy
• Method for generating engineered cardiac tissue with disease-causing mutation
• Method for modifying relaxation velocity of beating cardiomyocytes in culture
• Diagnostic aid in assessing causative mutations underlying cardiomyopathies

Advantages:

• High-throughput screening platform for therapeutic compounds for cardiomyopathy
• Identification of therapeutic target for early-onset restrictive cardiomyopathy
• Methodology to generate cell lines harboring disease mutation
• Compatible with study in both 2D and 3D culture systems
• Recapitulates various clinical phenotypes with an emphasis on calcium decay

Lead Inventor:

Barry Fine, M.D., Ph.D.

Patent Information:

Patent Pending (WO/2023/183371)

Related Publications:

• Wang BZ, Nash TR, Zhang X, Rao J, Abriola L, Kim Y, Zakharov S, Kim M, Luo LJ, Morsink M, Liu B, Lock RI, Fleischer S, Tamargo MA, Bohnen M, Welch CL, Chung WK, Marx SO, Surovtseva YV, Vunjak-Novakovic G, Fine BM. “Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery” Cell Rep Med. 2023 Mar 21; 4(3):100976.

Tech Ventures Reference:

• IR CU22246

• Licensing Contact: Kristin Neuman