Current treatments for Acanthamoeba keratitis rely on a combination of chlorhexidine gluconate, propamidine isethionate, and polyhexamethylene biguanide. These disinfectants are nonspecific and inherently toxic, which limits their effectiveness. Furthermore, in 10% of cases, recurrent infection ensues due to the difficulty in killing both trophozoites and double-walled cysts. Therefore, development of efficient, safe, and target-specific drugs which are capable of preventing recurrent Acanthamoeba infection is a critical unmet need for averting blindness. Since both trophozoites and cysts contain specific sets of membrane sterols, we hypothesized that antifungal drugs targeting sterol 14-demethylase (CYP51), known as conazoles, would have deleterious effects on A. castellanii trophozoites and cysts. To test this hypothesis, we first performed a systematic screen of the FDA-approved conazoles against A. castellanii trophozoites using a bioluminescence-based viability assay adapted and optimized for Acanthamoeba. The most potent drugs were then evaluated against cysts. Isavuconazole and posaconazole demonstrated low nanomolar potency against trophozoites of three clinical strains of A. castellanii. Furthermore, isavuconazole killed trophozoites within 24 h and suppressed excystment of preformed Acanthamoeba cysts into trophozoites. The rapid action of isavuconazole was also evident from the morphological changes at nanomolar drug concentrations causing rounding of trophozoites within 24 h of exposure. Given that isavuconazole has an excellent safety profile, is well tolerated in humans, and blocks A. castellanii excystation, this opens an opportunity for the cost-effective repurposing of isavuconazole for the treatment of primary and recurring Acanthamoeba keratitis.

Renal disease is a worldwide health issue. Besides transplantation, current therapies revolve around dialysis, which only delays disease progression but cannot replace other renal functions, such as synthesizing erythropoietin. To address these limitations, cell‐based approaches have been proposed to restore damaged kidneys as an alternative to current therapies. Recent studies have shown that stem cell‐derived secretomes can enhance tissue regeneration. However, many growth factors undergo rapid degradation when they are injected into the body in a soluble form. Efficient delivery and controlled release of secreting factors at the sites of injury would improve the efficacy in tissue regeneration. Herein, we developed a gel‐based delivery system for controlled delivery of trophic factors in the conditioned medium (CM) secreted from human placental stem cells (HPSCs) and evaluated the effect of trophic factors on renal regeneration. CM treatment significantly enhanced cell proliferation and survival in vitro. Platelet‐rich plasma (PRP) was used as a delivery vehicle for CM. Analysis of the release kinetics demonstrated that CM delivery through the PRP gel resulted in a controlled release of the factors both in vitro and in vivo. In an acute kidney injury model in rats, functional and structural analysis showed that CM delivery using the PRP gel system into the injured kidney minimized renal tissue damage, leading to a more rapid functional recovery when compared with saline, CM, or vehicle only injection groups. These results suggest that controlled delivery of HPSC‐derived trophic factors may provide efficient repair of renal tissue injury. stem cells translational medicine 2019;8:959&970