A dose-response study of thymosin β4 for the treatment of acute stroke

Morris DC, Cui Y, Cheung WL, Lu M, Zhang L, Zhang ZG, Chopp M · Journal of the Neurological Sciences

Neurological recovery improved significantly at 2 and 12 mg/kg out to day 56, while 18 mg/kg did not differ from control; the modelled optimum was 3.75 mg/kg. Lesion volume did not differ between any dose and control (p = 0.278, 0.085 and 0.957). The dose-response is an inverted U — the highest dose tested worked worst.

Population

Male Wistar rats after embolic middle cerebral artery occlusion; 50 randomised, 10 died within two days of the stroke and were excluded, 10 analysed per group

Intervention

Tβ4 2, 12 or 18 mg/kg intraperitoneally starting 24 h after stroke, then every three days for four more doses

Comparator

Vehicle

Limitations

Rat embolic stroke model, 10 animals per arm with behavioural testing blinded; no human stroke trial has followed. Tβ4 supplied by RegeneRx under a material-transfer agreement with the authors' institution, which has filed a patent on Tβ4 in neurological injury; NIH-funded. Directly relevant to dosing only as evidence that more is not reliably better.