Value Proposition
· High Diagnostic Sensitivity and Reproducibility: Detects a spatially diffuse molecular signature, defined by the upregulation of a distinct family of genes, enabling identification and stratification of myocarditis, of any sub-type
· Molecular Reframing of Disease: Redefines myocarditis as a diffuse molecular state of global myocardial inflammation with a common, diffuse gene expression signature, rather than a condition confined to discrete foci of immune infiltrates and myocyte damage
· Integration with Existing EMB Workflow: Compatible with standard EMB procedures and samples
· Non-Invasive Diagnostic and Therapy Development Potential: Accurate diagnosis based on molecular signatures offers new opportunities for myocarditis detection and targeted therapeutic development
Unmet Need
· According to UpToDate, the incidence of myocarditis has not been well defined, as clinical presentation is variable and there is a lack of accurate noninvasive diagnostic tests to screen for or confirm the diagnosis. In the United States, it is estimated that 10 to 20 individuals per 100,000 are diagnosed with myocarditis annually. This corresponds to approximately 33,000 to 66,000 new cases annually in the United States. Another study shows that across 204 countries and territories, there were 780,410 cases of myocarditis and 19,618 deaths in 1990. By 2019, there were 1,265,770 cases and 324,490 deaths (UpToDate, Mayo Clinic, BMC Public Health).
· The “gold standard” for diagnosing myocarditis is the histological analysis of endomyocardial biopsies (EMBx). However, EMBx can miss up to 50% of cases because it relies on visualizing inflammatory infiltrates and myocyte damage, which can be missed during random tissue sampling due to the patchy distribution of myocarditis. Some studies show that the sensitivity of EMBx may be as low as 10 to 35 percent due to variability in interpretation and sampling error.
· Cardiac MRI is commonly used in clinical practice to diagnose myocarditis, but it has very low sensitivity (about 60%) in rheumatologic patients on immunosuppression and sensitivity drops as time from onset of symptoms increases
· Thus, there exists a strong need to develop a sensitive, reliable diagnostic for myocarditis.
Technology Description
· The inability to provide a consistent and sensitive diagnosis of myocarditis has been a limiting factor in the development of effective treatments and accurate detection, hampering clinical trials for over 40 years.
· Researchers at Johns Hopkins found that cardiomyocytes exhibit a widespread, distinct transcriptomic signature, defined by upregulation of a distinct family of related genes, and developed a novel diagnostic tool for myocarditis with improved sensitivity and reproducibility.
· This study represents the first and most substantial tissue transcriptomic analysis of human myocarditis and borderline myocarditis to date, establishing a novel molecular framework for understanding myocarditis as a spatially diffuse and transcriptionally dynamic process, rather than confined to discrete histological lesions.
Stage of Development
· Proof of concept has been demonstrated and gene expression data has been validated in independent datasets; direct protein-level validation is ongoing ( not critical for diagnostic purposes)
Data Availability
· Data available upon request.
Publication
N/A
