From Patient Cells to Patient Care: Organ-on-a-Chip Research Helps Deliver New Hope for Children with Heart Disease
Article written by Jasleen Dhaliwal and Jennifer Doucet
From engineered heart tissues to real-world patient outcomes, Canadian researchers have shown how organ-on-a-chip technology can accelerate the path from discovery to treatment. A recent Phase 3 trial in adolescents with hypertrophic cardiomyopathy confirmed the effectiveness of mavacamten, building on earlier studies that used patient-specific cardiac tissues to predict the drug’s therapeutic potential. The trial also represents a remarkable example of how patient-specific organ-on-a-chip models can help bridge the gap between laboratory discovery and clinical care.
A Phase 3 trial on adolescent patients suffering from obstructive Hypertrophic cardiomyopathy (HCM), published in The New England Journal of Medicine (2026) has given new hope to pediatric patients suffering from debilitating heart disease. Led by Dr. Seema Mital at SickKids Hospital in Toronto, this patient trial is a strong demonstration of the power of precision medicine and its potential impact on patients. However, this story began years earlier, where teams at SickKids and the University of Toronto including the Mital lab, the Ellis lab, the Radisic lab and the Simmons lab, converted patient-derived cells collected from the Heart Centre Biobank and induced pluripotent stem cells (iPSCs). This work was enabled using the CRAFT facilities and resources, and was published in Cell Reports Medicine in 2024.
Graphical representation of the Biowire Platform. Figure from Zhao et al., 2020. Matrix Biol. 85–86 (189-204).
Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that causes heart muscle to thicken abnormally. It is the leading cause of heart failure and sudden cardiac death in children and adolescents. Since HCM is rooted in human genetics, animal models struggle to fully replicate what happens in real patients. To address this gap the team used the Biowire organ-on-a-chip platform developed by the Radisic lab at CRAFT, a system that builds three dimensional cardiac tissue, with HCM patient-derived cells. These cells are reprogrammed into iPSCs and then differentiated into cardiomyocytes that carry the exact mutations that caused the disease in the patient. Six weeks of electrical stimulation drives the tissue to maturity, allowing Biowire to generate measurable contractile force, unlike conventional 2-D cell cultures. This capability makes it a powerful tool for evaluating how a HCM heart responds to a drug.
Video: A Representative Movie of Biowire Contraction. Figure from Zhao et al., 2019. Cell. 176 (913-927.e18).
Work published in Cell Reports Medicine (2024) applied mavacamten to HCM Biowires from patients carrying mutations in MYH7 and MYBPC3, which encode proteins that regulate how heart muscle contracts. These mutations cause the heart to contract too forcefully, leading to abnormal thickening of the heart muscle over time. Animal models struggle to fully replicate human HCM due to differences in cardiac physiology, disease progression, and the complex genetic basis of the disease. However, the application of the drug mavacamten in the Biowire HCM models restored normal contractile function in patient cells carrying multiple different HCM mutations. It showed a more consistent and complete rescue of HCM abnormalities than existing standard drugs. This provided the foundational work for subsequent in-patient clinical studies.
Behind this breakthrough lies a story not just about a drug, but about a fundamentally new way of discovering and testing treatments. The SCOUT-HCM trial confirmed in real patients what the Biowire organ-on-chip experiments had already suggested. This trial is the first prospective evidence for a cardiac myosin inhibitor in a pediatric HCM population. At baseline, patients were well above the clinical threshold that defines obstruction. After 28 weeks on mavacamten, obstruction fell dramatically. Furthermore, improvements extended across multiple disease markers, including heart muscle wall thickness, cardiac biomarkers, exercise capacity, and functional symptoms. So, cardiac myosin inhibition works broadly across genetically diverse HCM.
This is just one example of how these organ-on-chip platforms can have a powerful impact on vulnerable patient populations. Engineered tissues can model diseases and evaluate drug responses with a precision that animal models alone often cannot provide, especially in cases such as these where there is no animal model available. The success of mavacamten illustrates how New Approach Methodologies (NAMs) can serve as incredibly powerful tools in the drug discovery pipeline. As platforms like Biowire continue to mature, they will become central tools in how the next generation of targeted therapies are brought to patients, translating discovery to clinical impact.