CalciMedica: CRACking toxicity

Calcineurin inhibitors are effective in preventing acute organ transplant rejection and treating autoimmune diseases, but their long-term use is associated with renal and hepatic toxicities. CalciMedica Inc. hopes to sidestep these toxicities by developing therapeutics that modulate calcium release-activated calcium channels, key upstream regulators of calcineurin activity.

Both of the calcineurin inhibitors approved to protect against transplant rejection have black box warnings. Prograf tacrolimus from Astellas Pharma Inc. (Tokyo:4503, Tokyo, Japan) has a warning for increased risk of hematological malignancies. The label for generic cyclosporin A warns of the potential for systemic hypertension and nephrotoxicity. Exactly how long-term inhibition of calcineurin generates these unwanted effects is not known...