Approximately 800,000 individuals suffer a stroke each year in the United States. Development of Glial Growth Factor 2 (GGF2) for promotion of stroke recovery is significant because of the lack of therapeutics to treat stroke. GGF2 also has a very wide treatment window (days) because it is not dependent upon neuroprotection. Additionally, as GGF2 is already in clinical trials for another indication, barries to manufacturing, formulation and toxicology have either been eliminated, or greatly reduced. The innovative aspect of this application comes from leveraging the existing development work that has been completed with GGF2 for another indication to efficiently enable an IND for stroke. Expanding on a significant body of preclinical data, GGF2 dosing will be optimized in a rat middle cerebral artery occlusion (MCAO) stroke model. Studies will explore dose frequency, extended dose duration and determine permanence of effects. Additional toxicology will be performed to enable the specific dose regimen proposed for stroke. GGF2 efficacy will then be confirmed in an established non-human primate model of cortical ischemia using a gyrencephalic rhesus monkey model. This model emphasizes neurorecovery rather than lesion volume reduction. Dosing will begin 24 hours after ischemia and behavioral improvements will be followed for at least 8 weeks in both rat and monkey studies. Following completion of studies in rhesus monkey an IND will be filed with the FDA.
GGF2 (neuregulin) is an exciting potential stroke therapeutic. It is able to protect the brain after stroke when perfusion is restored, and importantly, also promotes recovery in the absence of neuroprotection. This study will determine the efficacy of GGF2 in rodents via an MCAO stroke model, with confirmation studies in rhesus monkeys via a nonhuman primate model of cortical ischemia, resulting in a possible IND filing.