Ponericin-W-like 322

Objectives: There are no approved pharmacologic therapies for chronic sensorineural hearing loss (SNHL). The combination of CHIR99021+valproic acid (CV, FX-322) has been shown to regenerate mammalian cochlear hair cells ex vivo. The objectives were to characterize the cochlear pharmacokinetic profile of CV in guinea pigs, then measure FX-322 in human perilymph samples, and finally assess safety and audiometric effects of FX-322 in humans with chronic SNHL. Study designs: Middle ear residence, cochlear distribution, and elimination profiles of FX-322 were assessed in guinea pigs. Human perilymph sampling following intratympanic FX-322 dosing was performed in an open-label study in cochlear implant subjects. Unilateral intratympanic FX-322 was assessed in a Phase 1b prospective, randomized, double-blinded, placebo-controlled clinical trial. Setting: Three private otolaryngology practices in the US. Patients: Individuals diagnosed with mild to moderately severe chronic SNHL (≤70 dB standard pure-tone average) in one or both ears that was stable for ≥6 months, medical histories consistent with noise-induced or idiopathic sudden SNHL, and no significant vestibular symptoms. Interventions: Intratympanic FX-322. Main outcome measures: Pharmacokinetics of FX-322 in perilymph and safety and audiometric effects. Results: After intratympanic delivery in guinea pigs and humans, FX-322 levels in the cochlear extended high-frequency region were observed and projected to be pharmacologically active in humans. A single dose of FX-322 in SNHL subjects was well tolerated with mild, transient treatment-related adverse events (n = 15 FX-322 vs 8 placebo). Of the six patients treated with FX-322 who had baseline word recognition in quiet scores below 90%, four showed clinically meaningful improvements (absolute word recognition improved 18-42%, exceeding the 95% confidence interval determined by previously published criteria). No significant changes in placebo-injected ears were observed. At the group level, FX-322 subjects outperformed placebo group in word recognition in quiet when averaged across all time points, with a mean improvement from baseline of 18.9% (p = 0.029). For words in noise, the treated group showed a mean 1.3 dB signal-to-noise ratio improvement (p = 0.012) relative to their baseline scores while placebo-treated subjects did not (-0.21 dB, p = 0.71). Conclusions: Delivery of FX-322 to the extended high-frequency region of the cochlea is well tolerated and enhances speech recognition performance in multiple subjects with stable chronic hearing loss.

Riadh et al. Afr J Tradit Complement Altern Med. 2011;8(3):322-327. DETECTION AND EXTRACTION OF ANTI-LISTERIAL COMPOUNDS FROM CALLIGONUM COMOSUM, A MEDICINAL PLANT FROM ARID REGIONS OF TUNISIA. Riadh H, Imen F, Abdelmajid Z, Sinda F. Should read Hammami et al. Afr J Tradit Complement Altern Med. 2011;8(3):322-327. DETECTION AND EXTRACTION OF ANTI-LISTERIAL COMPOUNDS FROM CALLIGONUM COMOSUM, A MEDICINAL PLANT FROM ARID REGIONS OF TUNISIA. Hammami R, Farhat I, Zouhir A, Fedhila S[This corrects the article on p. 322 in vol. 8, PMID: 22468012.].

Humans have searched far beyond our planet to understand the fundamental principles and mechanisms of life [...].