Assessment of the neuroprotective efficacy of SBC003 in a mouse model of transient Middle Cerebral Artery Occlusion (tMCAO) - induced ischemic stroke.

The drug candidate, SBC003, has demonstrated neuroprotective and neurorescuing efficacy in pre-clinical ophthalmology models including rd10 mice and N-nitroso-N-methylurea - induced photoreceptor degeneration in mice. The therapeutic potential in stroke has not been investigated.

Cerebral Ischemia (CI) was induced in mice by tMCAO (intraluminal filament technique; 1 hr; Day 0) under isoflurane anesthesia. Animals (n=108) were allocated to sham or vehicle controls, edaravone/ dexborneol 10/2.5 mg/kg i.v. (Days 0 to 2; positive control) or SBC003 treatment groups. SBC003 (10, 50, 200 mg/kg p.o., OD) was administered under preventative (Days -3 to 0), therapeutic (Days 0 to 2), or continuous (Days -3 to 2) dosing regimens. Neurological functions (grip strength, balance beam, rotarod) were assessed on Days 1 and 2, and infarct area (2,3,5-triphenyltetrazolium chloride staining) on Day 2.

SBC003 exhibited dose-dependent reductions in infarct area (all treatment regimens). SBC003 as ‘therapeutic’ treatment exhibited highly significant effects at 200 mg/kg (15.1% vs. vehicle: 38.6%, p<0.001). Profound effects were measured following continuous dosing (200 mg/kg: 5.6% vs. vehicle: 36.5%, p<0.001 vs. edaravone/dexborneol: 13.2%, p<0.05).

Treatment with SBC003 (200 mg/kg) improved neurological functions as evidenced by a higher grip strength (205g vs. vehicle: 138g, p<0.001 vs. edaravone/dexborneol: 193g, p<0.05), faster balance beam crossing (31s vs. vehicle: 53s, p<0.01), and extended rotarod time (90s vs. vehicle: 38s, p<0.05) on Day 2.

SBC003 significantly reduced infarction and improved neurological functions following induction of ischemic stroke in mice. Importantly, SBC003 exhibited both preventative and therapeutic efficacy; it warrants further investigations as drug candidate with neuroprotective properties for the treatment of ischemic stroke.