cTnI (Cardiac Troponin-I)

Biology and Diseases

Cardiac Troponin-I (cTnI) is specific to cardiomyocytes and is released into blood following heart damage. Extensive studies have shown that cTnI, which is slowly released from damaged cardiomyocytes, often requires 4–8 hours post-trauma to be detectable. Measurement of cTnI concentrations in plasma/serum are the standard of care for diagnosing non-STEMI acute myocardial infarction (AMI). In addition, this biomarker has been widely accepted in preclinical and clinical drug development settings as an indicator of myocardial damage and hence, heart damage.

Therapies

cTnI is accepted as a biomarker to assess potential cardiotoxicity of experimental therapies. It is extensively studied in preclinical settings and included in clinical drug development programs when preclinical data suggests a potential for cardiac-related adverse events.

Unmet Need

Even though cTnI is used as the standard of care for diagnosing AMI, as well as in preclinical and clinical development, until recently its concentration in the plasma of apparently healthy humans and preclinical animal models had not been reported. Thus, it was impossible to benchmark a “normal” level within a given animal or human and measure small increases (velocity) of cTnI that might be associated with subtle cardiac damage. Furthermore, many assays do not equally quantify cTnI across different species and require large plasma sample volumes, limiting their use in preclinical settings, especially in rodent model systems.

Singulex Answer

Singulex’s cTnI assay, optimized for use on the Erenna System, provides cTnI quantification to 0.8 pg/mL (10%CV). The assay was designed to equilaterally quantify cTnI across humans, rats, dogs and monkeys.

Current ETAP investigators have used this assay to:

1. Define the concentration of plasma and serum cTnI in healthy humans, rats, dogs and monkeys .

2. Identify AMIs earlier in patients and in retrospective studies.

3. Measure heart damage earlier under physical stress or known cardiotoxins.

4. Study cTnI concentrations in a single rat using only 10 μL plasma.

This assay will allow investigators to:

1. Measure the potential cardiac safety and dosing of therapeutics in both preclinical and clinical settings.

2. Perform time-course studies using individual small animals or precious samples, when sample volume is an issue.

3. Design more robust clinical and preclinical studies when velocity of cTnI concentration change from a baseline normal level is used as an endpoint.

4. Understand how cTnI levels change from normal levels in a variety of cardiac-related diseases.

5. Understand the utility of cTnI as a biomarker to serve as a surrogate endpoint for clinical events.

Application Note

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