Purpose of review 

Genetic lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare, inherited, recessive disease, which manifests as two different syndromes: Familial LCAT deficiency (FLD) and Fish-eye disease (FED), characterized by low HDL-C and corneal opacity. FLD patients also develop anaemia and renal disease. There is currently no therapy for FLD, but novel therapeutics are at different stages of development. Here, we summarize the most recent advances and the opportunities for and barriers to the further development of such therapies.

Recent findings 

Recent publications highlight the heterogeneous phenotype of FLD and the uncertainty over the natural history of disease and the factors contributing to disease progression. Therapies that restore LCAT function (protein and gene replacement therapies and LCAT activators) showed promising effects on markers of LCAT activity. Although they do not restore LCAT function, HDL mimetics may slow renal disease progression.

Summary 

The further development of novel therapeutics requires the identification of efficacy endpoints, which include quantitative biomarkers of disease progression. Because of the heterogeneity of renal disease progression among FLD individuals, future treatments for FLD will have to be tailored based on the specific clinical characteristics of the patient. Extensive studies of the natural history and biomarkers of the disease will be required to achieve this goal.

中文翻译：

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家族性卵磷脂：胆固醇酰基转移酶缺乏症的新治疗机会：前景与挑战

审查目的 

遗传性卵磷脂：胆固醇酰基转移酶 (LCAT) 缺乏症是一种罕见的遗传性隐性疾病，表现为两种不同的综合征：家族性 LCAT 缺乏症 (FLD) 和鱼眼病 (FED)，其特征为低 HDL-C 和角膜混浊。FLD 患者还会出现贫血和肾脏疾病。目前尚无针对 FLD 的治疗方法，但新疗法正处于不同的开发阶段。在这里，我们总结了此类疗法的最新进展以及进一步发展的机遇和障碍。

最近的发现 

最近的出版物强调了 FLD 的异质表型以及疾病自然史和导致疾病进展的因素的不确定性。恢复 LCAT 功能的疗法（蛋白质和基因替代疗法以及 LCAT 激活剂）对 LCAT 活性标记物显示出有希望的效果。尽管 HDL 模拟物不能恢复 LCAT 功能，但它们可能会减缓肾脏疾病的进展。

概括 

新疗法的进一步开发需要确定疗效终点，其中包括疾病进展的定量生物标志物。由于 FLD 个体之间肾脏疾病进展的异质性，未来的 FLD 治疗必须根据患者的具体临床特征进行定制。为了实现这一目标，需要对该疾病的自然史和生物标志物进行广泛的研究。