{"title":"Long-term Safety Pharmacology and Musculoskeletal Changes of HMGB1 Box A Gene Therapy in Middle-aged Monkeys.","authors":"Sukanya Jaroenporn, Tayanee Chundee, Sakawdaurn Yasom, Lalitta Suriya-Arunroj, Motee Chimngam, Nutchanat Suttisan, Suchinda Malaivijitnond, Apiwat Mutirangura","doi":"10.21873/invivo.13994","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>HMGB1 Box A gene therapy is a promising therapeutic approach for age-associated diseases, based on evidence from <i>in vitro</i> and <i>in vivo</i> studies in rodents. This study aimed to evaluate long-term safety and musculoskeletal change of the Box A gene in non-human primates.</p><p><strong>Materials and methods: </strong>Perimenopausal monkeys were intravenously injected with a control plasmid (PC group) or Box A plasmid (Box A group) once a week for eight weeks, and were observed for one year. The safety pharmacology, blood biochemistry and hematology, bone mineral density, bone geometry, and muscle density were assessed and compared between the groups.</p><p><strong>Results: </strong>The safety pharmacological tests, general clinical observations, and evaluation of the central nervous, cardiovascular, and respiratory systems revealed no safety concerns. The response of the musculoskeletal system to Box A showed that the radius and tibia exhibited opposing bone density and size changes between the PC and Box A groups. Box A attenuated the age-related increase in bone mass and decrease in bone size at the radial metaphysis. Box A promoted cortical bone accumulation in the tibial diaphysis. The PC group, but not the Box A group, showed elevated blood glucose levels starting from the 48<sup>th</sup> week of the experiment. Box A group trended to gain less weight than the PC group, without experiencing muscle loss.</p><p><strong>Conclusion: </strong>This study indicated that Box A was safe over a 56-week observation period, causing no adverse clinical symptoms. Notably, it mitigated age-associated phenotypes, including improved bone health, lowered blood glucose, and reduced weight gain in perimenopausal monkeys. These results suggest Box A as a safe rejuvenation medicine.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"1965-1983"},"PeriodicalIF":1.8000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223620/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"In vivo","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/invivo.13994","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background/aim: HMGB1 Box A gene therapy is a promising therapeutic approach for age-associated diseases, based on evidence from in vitro and in vivo studies in rodents. This study aimed to evaluate long-term safety and musculoskeletal change of the Box A gene in non-human primates.
Materials and methods: Perimenopausal monkeys were intravenously injected with a control plasmid (PC group) or Box A plasmid (Box A group) once a week for eight weeks, and were observed for one year. The safety pharmacology, blood biochemistry and hematology, bone mineral density, bone geometry, and muscle density were assessed and compared between the groups.
Results: The safety pharmacological tests, general clinical observations, and evaluation of the central nervous, cardiovascular, and respiratory systems revealed no safety concerns. The response of the musculoskeletal system to Box A showed that the radius and tibia exhibited opposing bone density and size changes between the PC and Box A groups. Box A attenuated the age-related increase in bone mass and decrease in bone size at the radial metaphysis. Box A promoted cortical bone accumulation in the tibial diaphysis. The PC group, but not the Box A group, showed elevated blood glucose levels starting from the 48th week of the experiment. Box A group trended to gain less weight than the PC group, without experiencing muscle loss.
Conclusion: This study indicated that Box A was safe over a 56-week observation period, causing no adverse clinical symptoms. Notably, it mitigated age-associated phenotypes, including improved bone health, lowered blood glucose, and reduced weight gain in perimenopausal monkeys. These results suggest Box A as a safe rejuvenation medicine.
期刊介绍:
IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management.
The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.