Pub Date : 2024-09-07DOI: 10.1016/S0140-6736(24)01447-8
Paul Yang, Laura P Pardon, Allen C Ho, Andreas K Lauer, Dan Yoon, Shannon E Boye, Sanford L Boye, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Malgorzata Swider, Iryna Viarbitskaya, Tomas S Aleman, Mark E Pennesi, Christine N Kay, Kenji P Fujita, Artur V Cideciyan
Background: Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.
Methods: 15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study. All patients received unilateral subretinal injections of ATSN-101. In the dose-escalation phase, three adult cohorts (n=3 each) were treated with three ascending doses: 1·0 × 1010 vg/eye (low dose), 3·0 × 1010 vg/eye (middle dose), and 1·0 × 1011 vg/eye (high dose). In the dose-expansion phase, one adult cohort (n=3) and one paediatric cohort (n=3) were treated at the high dose. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints included full-field stimulus test (FST) and best-corrected visual acuity (BCVA). A multi-luminance mobility test (MLMT) was also done. Data through the 12-month main study period are reported.
Findings: Patients were enrolled between Sept 12, 2019, and May 5, 2022. A total of 68 TEAEs were observed, 56 of which were related to the surgical procedure. No serious TEAE was related to the study drug. Ocular inflammation was mild and reversible with steroid treatment. For patients who received the high dose, mean change in dark-adapted FST was 20·3 decibels (dB; 95% CI 6·6 to 34·0) for treated eyes and 1·1 dB (-3·7 to 5·9) for untreated eyes at month 12 (white stimulus); improvements were first observed at day 28 and persisted over 12 months (p=0·012). Modest improvements in BCVA were also observed (p=0·10). Three of six patients who received the high dose and did the MLMT achieved the maximum score in the treated eye.
Interpretation: ATSN-101 is well tolerated 12 months after treatment, with no drug-related serious adverse events. Clinically significant improvements in retinal sensitivity were sustained in patients receiving the high dose.
{"title":"Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study.","authors":"Paul Yang, Laura P Pardon, Allen C Ho, Andreas K Lauer, Dan Yoon, Shannon E Boye, Sanford L Boye, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Malgorzata Swider, Iryna Viarbitskaya, Tomas S Aleman, Mark E Pennesi, Christine N Kay, Kenji P Fujita, Artur V Cideciyan","doi":"10.1016/S0140-6736(24)01447-8","DOIUrl":"10.1016/S0140-6736(24)01447-8","url":null,"abstract":"<p><strong>Background: </strong>Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.</p><p><strong>Methods: </strong>15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study. All patients received unilateral subretinal injections of ATSN-101. In the dose-escalation phase, three adult cohorts (n=3 each) were treated with three ascending doses: 1·0 × 10<sup>10</sup> vg/eye (low dose), 3·0 × 10<sup>10</sup> vg/eye (middle dose), and 1·0 × 10<sup>11</sup> vg/eye (high dose). In the dose-expansion phase, one adult cohort (n=3) and one paediatric cohort (n=3) were treated at the high dose. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints included full-field stimulus test (FST) and best-corrected visual acuity (BCVA). A multi-luminance mobility test (MLMT) was also done. Data through the 12-month main study period are reported.</p><p><strong>Findings: </strong>Patients were enrolled between Sept 12, 2019, and May 5, 2022. A total of 68 TEAEs were observed, 56 of which were related to the surgical procedure. No serious TEAE was related to the study drug. Ocular inflammation was mild and reversible with steroid treatment. For patients who received the high dose, mean change in dark-adapted FST was 20·3 decibels (dB; 95% CI 6·6 to 34·0) for treated eyes and 1·1 dB (-3·7 to 5·9) for untreated eyes at month 12 (white stimulus); improvements were first observed at day 28 and persisted over 12 months (p=0·012). Modest improvements in BCVA were also observed (p=0·10). Three of six patients who received the high dose and did the MLMT achieved the maximum score in the treated eye.</p><p><strong>Interpretation: </strong>ATSN-101 is well tolerated 12 months after treatment, with no drug-related serious adverse events. Clinically significant improvements in retinal sensitivity were sustained in patients receiving the high dose.</p><p><strong>Funding: </strong>Atsena Therapeutics.</p>","PeriodicalId":98,"journal":{"name":"Photochemical & Photobiological Sciences","volume":"404 10456","pages":"962-970"},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07Epub Date: 2024-08-30DOI: 10.1016/S0140-6736(24)01763-X
Camilla Hage
{"title":"GLP-1 receptor agonists in heart failure: how far to expand use?","authors":"Camilla Hage","doi":"10.1016/S0140-6736(24)01763-X","DOIUrl":"10.1016/S0140-6736(24)01763-X","url":null,"abstract":"","PeriodicalId":98,"journal":{"name":"Photochemical & Photobiological Sciences","volume":" ","pages":"909-911"},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07Epub Date: 2024-08-31DOI: 10.1016/S0140-6736(24)01678-7
Giulio G Stefanini, Angelo Oliva
{"title":"Is this the conclusive evidence for ticagrelor monotherapy in acute coronary syndromes?","authors":"Giulio G Stefanini, Angelo Oliva","doi":"10.1016/S0140-6736(24)01678-7","DOIUrl":"10.1016/S0140-6736(24)01678-7","url":null,"abstract":"","PeriodicalId":98,"journal":{"name":"Photochemical & Photobiological Sciences","volume":" ","pages":"908-909"},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07Epub Date: 2024-08-29DOI: 10.1016/S0140-6736(24)01680-5
Dongju Shin, Dong-Jin Shin
{"title":"6 months on: South Korean medical students still on leave.","authors":"Dongju Shin, Dong-Jin Shin","doi":"10.1016/S0140-6736(24)01680-5","DOIUrl":"10.1016/S0140-6736(24)01680-5","url":null,"abstract":"","PeriodicalId":98,"journal":{"name":"Photochemical & Photobiological Sciences","volume":" ","pages":"932"},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/S0140-6736(24)01550-2
Jeremy W Jacobs, Imelda Bates, Claudia S Cohn, Nabajyoti Choudhury, Shirley Owusu-Ofori, Hans Vrielink, Eshan U Patel, Silvano Wendel, Aaron A R Tobian, Evan M Bloch
The optimum number of units of blood and the associated number of blood donors required to meet a given population's needs remain undetermined globally. Typically, a whole blood donation rate of ten donations per 1000 population, at a minimum, is necessary to meet a country's blood needs. This rate is attributed to a WHO recommendation that 1% of a given country's population should donate blood to ensure a blood supply that is sufficient to meet clinical needs. This often cited metric was first referenced in a 1971 WHO report, yet neither supporting data or references were provided, suggesting that it was flawed at its founding. Regardless, this metric does not provide an accurate or contemporary determination of blood needs, which has ramifications for health service provision and planning, particularly in low-income and lower-middle-income countries. Modelling studies that account for geographical variability in disease burden, health-care infrastructure, and transfusion practices are needed to accurately estimate blood needs. A paucity of data to inform modelling remains a major obstacle in this regard. We discuss the history of the global blood donation index and highlight some factors that should be considered to better understand contemporary blood needs.
{"title":"The global blood donation index: an imperfect measure of transfusion need.","authors":"Jeremy W Jacobs, Imelda Bates, Claudia S Cohn, Nabajyoti Choudhury, Shirley Owusu-Ofori, Hans Vrielink, Eshan U Patel, Silvano Wendel, Aaron A R Tobian, Evan M Bloch","doi":"10.1016/S0140-6736(24)01550-2","DOIUrl":"10.1016/S0140-6736(24)01550-2","url":null,"abstract":"<p><p>The optimum number of units of blood and the associated number of blood donors required to meet a given population's needs remain undetermined globally. Typically, a whole blood donation rate of ten donations per 1000 population, at a minimum, is necessary to meet a country's blood needs. This rate is attributed to a WHO recommendation that 1% of a given country's population should donate blood to ensure a blood supply that is sufficient to meet clinical needs. This often cited metric was first referenced in a 1971 WHO report, yet neither supporting data or references were provided, suggesting that it was flawed at its founding. Regardless, this metric does not provide an accurate or contemporary determination of blood needs, which has ramifications for health service provision and planning, particularly in low-income and lower-middle-income countries. Modelling studies that account for geographical variability in disease burden, health-care infrastructure, and transfusion practices are needed to accurately estimate blood needs. A paucity of data to inform modelling remains a major obstacle in this regard. We discuss the history of the global blood donation index and highlight some factors that should be considered to better understand contemporary blood needs.</p>","PeriodicalId":98,"journal":{"name":"Photochemical & Photobiological Sciences","volume":"404 10456","pages":"988-990"},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07Epub Date: 2024-08-29DOI: 10.1016/S0140-6736(24)01713-6
Yamina Boukari, Delan Devakumar
{"title":"Far-right riots in the UK: the culmination of years of rhetoric and policies.","authors":"Yamina Boukari, Delan Devakumar","doi":"10.1016/S0140-6736(24)01713-6","DOIUrl":"10.1016/S0140-6736(24)01713-6","url":null,"abstract":"","PeriodicalId":98,"journal":{"name":"Photochemical & Photobiological Sciences","volume":" ","pages":"931"},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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