Volume 9 Issue 5, May 2024

ISSN: 2095-9907 

EISSN: 2059-23635 

2023 impact factor 40.8 

 (Clarivate Analytics, 2024)
Volume 9 Issue 5, May 2024:
Article
Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial
Jinyuan Wang  ORCID: orcid.org/0000-0002-8378-1249,Jinlu Zhang,Shicheng Yu,Hongyan Li,Shaohong Chen,Jingting Luo,Haibo Wang,Yuxia Guan,Haihan Zhang,Shiyi Yin  ORCID: orcid.org/0000-0001-9119-0302,Huili Wang,Heping Li,Junle Liu,Jingyuan Zhu,Qiong Yang,Ying Sha,Chuan Zhang,Yuhang Yang,Xuan Yang,Xifang Zhang,Xiuli Zhao,Likun Wang  ORCID: orcid.org/0000-0002-0933-2808,Liping Yang &…Wenbin Wei  ORCID: orcid.org/0000-0003-2386-0989 
Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180–365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients’ improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).