PDF(Pubmed)
Abstract：
OBJECTIVE: Leber congenital amaurosis due to CEP290 mutations (LCA10) is an inherited retinal disease that often results in severe visual impairment or blindness in early childhood. Currently, there are no approved treatments, highlighting the considerable unmet medical need associated with LCA10. We aimed to review the clinical characteristics of LCA10, its impact on patients and society, and the investigational treatment strategies currently in development.
METHODS: Review of the current literature.
RESULTS: LCA10 is an autosomal recessive ciliopathy, for which the CEP290 intronic variant c.2991+1655A>G (p.Cys998X) is the most common mutation. Usually diagnosed in early childhood, most patients with LCA10 have severe visual impairment during their first decade of life, which significantly affects the quality of life and development. LCA10 also has a significant societal burden (direct and indirect costs). RNA editing using antisense oligonucleotides or Staphylococcus aureus CRISPR-associated protein-9 nuclease is currently under investigation for treatment of p.Cys998X LCA10. Specifically, the antisense oligonucleotide therapy QR-110 (sepofarsen) has demonstrated encouraging safety and efficacy data in a first-in-human trial; a phase 3 clinical trial is ongoing.
CONCLUSIONS: Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve the patient quality of life and reduce burden of disease.
METHODS: Review of the current literature.
RESULTS: LCA10 is an autosomal recessive ciliopathy, for which the CEP290 intronic variant c.2991+1655A>G (p.Cys998X) is the most common mutation. Usually diagnosed in early childhood, most patients with LCA10 have severe visual impairment during their first decade of life, which significantly affects the quality of life and development. LCA10 also has a significant societal burden (direct and indirect costs). RNA editing using antisense oligonucleotides or Staphylococcus aureus CRISPR-associated protein-9 nuclease is currently under investigation for treatment of p.Cys998X LCA10. Specifically, the antisense oligonucleotide therapy QR-110 (sepofarsen) has demonstrated encouraging safety and efficacy data in a first-in-human trial; a phase 3 clinical trial is ongoing.
CONCLUSIONS: Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve the patient quality of life and reduce burden of disease.
摘要：
目的：由于CEP290突变导致的Leber先天性黑蒙（LCA10）是一种遗传性视网膜疾病，通常在儿童早期导致严重的视力障碍或失明。目前,没有批准的治疗方法，突出了与LCA10相关的相当大的未满足的医疗需求。我们的目的是回顾LCA10的临床特点，其对患者和社会的影响，以及目前正在制定的研究性治疗策略。
方法：综述现有文献。
结果：LCA10是一种常染色体隐性遗传性纤毛病，对于CEP290内含子变体c.2991+1655A>G(p.Cys998X）是最常见的突变。通常在儿童早期被诊断出来，大多数LCA10患者在生命的第一个十年都有严重的视力障碍，严重影响生活质量和发展。LCA10还具有重大的社会负担(直接和间接成本)。目前正在研究使用反义寡核苷酸或金黄色葡萄球菌CRISPR相关蛋白9核酸酶进行RNA编辑以治疗p.Cys998XLCA10。具体来说,反义寡核苷酸疗法QR-110(sepofarsen)在一项首次人体试验中证明了令人鼓舞的安全性和有效性数据;一项3期临床试验正在进行中.
结论：可以保持或改善LCA10患者视力的干预措施在改善患者生活质量和减轻疾病负担方面具有相当大的潜力。
方法：综述现有文献。
结果：LCA10是一种常染色体隐性遗传性纤毛病，对于CEP290内含子变体c.2991+1655A>G(p.Cys998X）是最常见的突变。通常在儿童早期被诊断出来，大多数LCA10患者在生命的第一个十年都有严重的视力障碍，严重影响生活质量和发展。LCA10还具有重大的社会负担(直接和间接成本)。目前正在研究使用反义寡核苷酸或金黄色葡萄球菌CRISPR相关蛋白9核酸酶进行RNA编辑以治疗p.Cys998XLCA10。具体来说,反义寡核苷酸疗法QR-110(sepofarsen)在一项首次人体试验中证明了令人鼓舞的安全性和有效性数据;一项3期临床试验正在进行中.
结论：可以保持或改善LCA10患者视力的干预措施在改善患者生活质量和减轻疾病负担方面具有相当大的潜力。
