Camizestrant causes reversible pharmacological effects on retinal responses in rats

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-09-22 DOI:10.1016/j.tranon.2025.102539

Gregory Hamm , Gareth Maglennon , Stuart Purbrick , Lucy Flint , Glen Hawthorne , James Atkinson , Ruth Macdonald , Alexander Harmer , Stewart Jones , Yelena Krakova , James Ver Hoeve , Andrew Walding , Lindsay Wright

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引用次数: 0

Abstract

Some patients treated with camizestrant in the SERENA-1 and SERENA-2 clinical trials experienced mild, transient, reversible visual effects. This nonclinical investigation used electroretinograms (ERGs) and mass spectrometry imaging to examine the effect of camizestrant on retinal responses in rats and to investigate the origin of the visual effects observed in humans.

Mass spectrometry imaging was used to confirm the presence of camizestrant in the retina of rats following 7 consecutive days of dosing (75 mg kg^-1/day). A separate group of rats then received doses of either camizestrant (5, 12, 25, or 75 mg kg^-1/day) or control over 7 consecutive days. They were observed for 7 additional days without further dosing. ERGs were conducted at baseline, Days 1 and 7, and 7 days after last dose to assess changes in retinal responses. Ophthalmic examinations were conducted pre-dose and on Days 8 and 15.

Administration of camizestrant at ≥12 mg kg^-1/day significantly reduced dark-adapted ERG b-waves and oscillatory potential amplitudes, increased light-adapted b-wave amplitude and latency, and reduced the rate of light adaptation. All observed effects were dose dependent and reversible, returning to baseline levels a week after post-dose washout. There was no evidence of any structural changes in the eye.

The results support a reversible, pharmacological effect of camizestrant on retinal responses in the absence of structural changes and are consistent with clinical findings. These data offer insight into the potential mechanism of the visual effects observed in patients.

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Camizestrant对大鼠视网膜反应产生可逆的药理作用

在SERENA-1和SERENA-2临床试验中，一些接受camizestrant治疗的患者出现了轻微的、短暂的、可逆的视觉效果。这项非临床研究使用视网膜电图（ERGs）和质谱成像来检查camizestrant对大鼠视网膜反应的影响，并调查在人类中观察到的视觉效果的来源。在连续给药7天（75 mg kg-1/天）后，采用质谱成像法确认卡米司腾在大鼠视网膜中的存在。然后，另一组大鼠连续7天服用卡米司腾（5、12、25或75 mg kg-1/天）或对照组。他们在没有进一步给药的情况下观察了7天。在基线、第1天和第7天以及末次给药后7天进行ERGs以评估视网膜反应的变化。给药前、第8天和第15天分别进行眼科检查。camizestrant≥12 mg kg-1/天显著降低暗适应ERG b波和振荡电位振幅，增加光适应b波振幅和潜伏期，降低光适应速率。所有观察到的效应都是剂量依赖性和可逆的，在给药后洗脱一周后恢复到基线水平。没有证据表明眼睛有任何结构变化。该结果支持在没有结构改变的情况下，camizestrant对视网膜反应具有可逆的药理作用，并且与临床结果一致。这些数据为观察到的患者视觉效果的潜在机制提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.