Cross-Species Cardiac Prediction

From Animal Model Data to Human Cardiac Prediction – Without Refitting

The core challenge after every preclinical study:

Rodents express predominantly α-MHC (fast myosin). Humans express predominantly β-MHC (slow myosin).

A drug that reduces contractility by 30% in a rat will not produce the same 30% effect in humans because the kinetic parameters of the myosin motor are fundamentally different. Not just quantitatively, but mechanistically.

Standard CRO animal studies cannot account for this difference.

Myosin isoform composition by species:

• Mouse — α-MHC: ~100%; β-MHC: ~0%
• Rat — α-MHC: ~75%; β-MHC: ~25%
• Human — α-MHC: ~5%; β-MHC: ~95%

How MUSICO handles this:

Reference:
Prodanovic et al., Int J Mol Sci 23(3):1135, 2022