Propranolol as therapy for cerebral cavernous malformations: a cautionary note

Oldenburg and coworkers [2] showed that propranolol decreased lesion development and rescued barrier function in CCMs in Ccm3/(Pdcd10)iECKO model of CCM disease when given propranolol orally at 12.5 mg/kg/day (equivalent to 70 mg/day for a 70 kg human adult [3, 4]) up to age P21 via mother’s milk, and then at 100 mg/kg/day (equivalent to 560 mg/day for a 70 kg human adult [3, 4]) from ages P21 to P28. Methods to acquire and analyze data for hemodynamics (contractility and heart rate), lesion burden (percent lesion volume per mouse brain volume, primary outcome), acute and chronic hemorrhage, and attrition were described previously [5]. Propranolol treatment at 15 mg/kg/day did not affect CCM lesion burden (Fig. 1c, d), acute hemorrhage (Fig. 1e), chronic hemorrhage (scant Perls stained non-heme iron in 4 out of 29 placebo and in 2 out of 26 propranolol treated mice) nor attrition (Fig. 1f).