Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

“…Anti‐HMGB1 mAb treatment attenuates maximal electroshock and pentylenetetrazol induced acute seizures, as well as inhibits the translocation and/or release of HMGB1 in astrocytes and neurons, as evidenced by demonstration of HMGB1 confined to cell nuclei (Zhao et al . ). But anti‐HMGB1 mAb did not demonstrate any anti‐seizure effect on TLR4 KO mice, which supports the notion that the HMGB1‐TLR4 regulatory axis contributes to ictogenesis (Zhao et al .…”

“…But anti‐HMGB1 mAb did not demonstrate any anti‐seizure effect on TLR4 KO mice, which supports the notion that the HMGB1‐TLR4 regulatory axis contributes to ictogenesis (Zhao et al . ). The anti‐seizure effect of anti‐HMGB1 mAb in the KA‐induced seizure model and in the brain slices obtained from surgical resection of clinically drug‐resistant human patients suggest that anti‐HMGB1 mAb exhibits significant clinical therapeutic value for patients with medically refractory TLE (Zhao et al .…”

“…The anti‐seizure effect of anti‐HMGB1 mAb in the KA‐induced seizure model and in the brain slices obtained from surgical resection of clinically drug‐resistant human patients suggest that anti‐HMGB1 mAb exhibits significant clinical therapeutic value for patients with medically refractory TLE (Zhao et al . ). A limited number of studies have also demonstrated the neuroprotective role of anti‐HMGB1 Ab in neuronal damage and inflammation after SE.…”

“…Moreover, the anti‐epileptic potential of anti‐HMGB1 mAb on the human epileptic brain slices has not to be washed out implicating that anti‐HMGB1 mAb binds solidly with HMGB1 solidly and has promising potentially long‐term anti‐epileptic activity (Zhao et al . ). In regards to the safety profile of anti‐HMGB1 mAb, it only targets the activated, translocated HMGB1, and even in a high dose (25 mg/kg in mice) did not show any impairment in basic physical functions, body growth rate and thermoregulation (Zhao et al .…”

Pharmacological targeting of brain inflammation in epilepsy: Therapeutic perspectives from experimental and clinical studies

“…Notably, these treatments mediated therapeutic effects outlasting drug withdrawal, and therefore supported disease‐modification, rather than purely symptomatic, effects. Similarly, the transient administration of an anti‐HMGB1 monoclonal antibody in mice during epileptogenesis resulted in disease‐modifying effects consisting of a significant reduction in spontaneous seizure frequency and improvement of cognitive deficits .…”