Cimaglermin (
neuregulin 1β3,
glial growth factor 2) is a
neuregulin growth factor family member in clinical development for chronic
heart failure. Previously, in a permanent
middle cerebral artery occlusion (pMCAO) rat
stroke model, systemic
cimaglermin treatment initiated up to 7 days after
ischemia onset promoted recovery without reduced lesion volume. Presented here to extend the evidence are two studies that use a rat
stroke model to evaluate the effects of
cimaglermin dose level and dose frequency initiated 24 hr after pMCAO. Forelimb- and hindlimb-placing scores (proprioceptive behavioral tests), body-swing symmetry, and
infarct volume were compared between treatment groups (n = 12/group). Possible mechanisms underlying
cimaglermin-mediated neurologic recovery were examined through axonal growth and synapse formation histological markers.
Cimaglermin was evaluated over a wider dose range (0.02, 0.1, or 1.0 mg/kg) than doses previously shown to be effective but used the same dosing regimen (2 weeks of daily
intravenous administration, then 1 week without treatment). The dose-frequency study used the dose-ranging study's most effective dose (1.0 mg/kg) to compare daily, once per week, and twice per week dosing for 3 weeks (then 1 week without treatment). Dose- and frequency-dependent functional improvements were observed with
cimaglermin without reduced lesion volume.
Cimaglermin treatment significantly increased
growth-associated protein 43 expression in both hemispheres (particularly somatosensory and motor cortices) and also increased
synaptophysin expression. These data indicate that
cimaglermin enhances recovery after
stroke. Immunohistochemical changes were consistent with axonal sprouting and synapse formation but not acute neuroprotection.
Cimaglermin represents a potential clinical development candidate for
ischemic stroke treatment.