Comparison between sodium iodate and lipid peroxide murine models of age-related macular degeneration for drug evaluation—a narrative review

Kim, Soo‐Young; Qian, Haohua

doi:10.21037/aes-21-25

Cited by 1 publication

(2 citation statements)

References 62 publications

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“…Systemic injection of sodium iodate induced rapid RPE degeneration [ 24 , 25 ]. Mice administered sodium iodate intravenously exhibited various pathological features, including RPE and photoreceptor degeneration, as well as RPE movement [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

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Pre-Clinical Studies of a Novel Bispecific Fusion Protein Targeting C3b and VEGF in Neovascular and Nonexudative AMD Models

Lee,

Kim,

Chung

et al. 2024

Ophthalmol Ther

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Introduction KNP-301 is a bi-specific fragment crystallizable region (Fc) fusion protein, which inhibits both C3b and vascular endothelial growth factor (VEGF) simultaneously for patients with late-stage age-related macular degeneration (AMD). The present study evaluated in vitro potency, in vivo efficacy, intravitreal pharmacokinetics (IVT PK), and injectability of KNP-301. Methods C3b and VEGF binding of KNP-301 were assessed by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA), and cellular bioassays. A laser-induced choroidal neovascularization (CNV) model and a sodium iodate-induced nonexudative AMD model were used to test the in vivo efficacy of mouse surrogate of KNP-301. Utilizing fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) scans, the reduction in disease lesions were analyzed in a CNV mouse model. In the nonexudative AMD mouse model, outer nuclear layer (ONL) was assessed by immunofluorescence staining. Lastly, intravitreal pharmacokinetic study was conducted with New Zealand white rabbits via IVT administration of KNP-301 and injectability of KNP-301 was examined by a viscosity test at high concentrations. Results KNP-301 bound C3b selectively, which resulted in a blockade of the alternative pathway, not the classical pathway. KNP-301 also acted as a VEGF trap, impeding VEGF-mediate signaling. Our dual-blockade strategy was effective in both neovascular and nonexudative AMD models. Moreover, KNP-301 had an advantage of potentially less frequent dosing due to the long half-life in the intravitreal chamber. Our viscosity assessment confirmed that KNP-301 meets the criteria of the IVT injection. Conclusions Unlike current therapies, KNP-301 is expected to cover patients with late-stage AMD of both neovascular and nonexudative AMD, and its long-term PK profile at the intravitreal chamber would allow convenience in the dosing interval of patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-024-00982-3.

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Section: Resultsmentioning

confidence: 99%

“…Several in vivo models were employed for nonexudative age-related macular degeneration [24][25][26]. In this study, the sodium iodateinduced nonexudative AMD mouse model was utilized.…”

Section: Efficacy Of Mknp-301 On Mouse Nonexudative Amd Modelmentioning

confidence: 99%