Patent Evaluation: Treatment of neurological disorders with IL-antagonists

Abstract

Novelty: The use of lipocortin (preferrably being lipocortin- 1 or a fragment) for the treatment of neurodegeneration is claimed. Lipocortin-1 is a naturally occuring protein and an active fragment has been identified which has one hundred and eighty-eight amino acids. This fragment inhibits neurological damage and some actions of IL-1 in the brain. It is suggested that its neuroprotective effect may be due to inhibition of IL-1.

Biology: In a middle cereral artery occlusion model in the rat, the active fragment (given icv) showed 70% reduction in lesion size 30 mins after occlusion and 25% reduction when given 60 mins after occlusion. Also the active fragment markedly inhibited excitotoxic brain damage caused by an NMDA agonist (cis-2,4-methanoglutamate).

Chemistry: The structure of lipocortin-1 is described in Pepinsky et al. J. B i d . Chem. (1988) 263: 97-103.