A novel treatment for vestibular disorder with FGLM-NH2 plus SSSR

Abstract

Topical FGLM-NH2 (Phenylalanine–Glycine–Leucine–Methionine–Amide) plus SSSR (Serine–Serine–Serine–Arginine) facilitates recovery from vestibular disorders induced by (±)-α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) in guinea pigs and might offer a treatment strategy for patients with peripheral vestibular disorders.The tetrapeptide FGLM-NH2 derived from substance P (SP) can be used to treat corneal disorders when combined with SSSR, which is a tetrapeptide derived from insulin-like growth factor-1 (IGF-1). We examined the influence of FGLM-NH2 plus SSSR when locally applied to the unilateral inner ear of guinea pigs with vestibular disorder induced by AMPA. A total of 18 Hartley white guinea pigs were assigned to groups receiving either FGLM-NH2 plus SSSR, artificial perilymph, or no treatment at all. A hole was drilled adjacent to the round window, with AMPA then infused into the hole in order to induce the vestibular disorder. Thereafter, FGLM-NH2 plus SSSR or artificial perilymph was delivered via an osmotic pump that was inserted into the hole. Sinusoidal rotation tests were used for observing spontaneous nystagmus and for measurements of the vestibulo-ocular reflexes (VOR). Two animals from each group were immunohistochemically examined at 24h after the treatment. Spontaneous nystagmus decreased immediately after FGLM-NH2 plus SSSR infusion. The recovery of the VOR gains was statistically faster than that seen in the control group at 3 and 7 days after treatment. Immunohistochemical examination revealed that many synaptic ribbons, which are markers of the synapse, were stained in the FGLM-NH2 plus SSSR group compared with the untreated group. Topical application of FGLM-NH2 plus SSSR accelerates functional recovery from AMPA-induced vestibular disorders by facilitating synaptic regeneration in guinea pigs.