Jaroenporn Sukanya, Chundee Tayanee, Yasom Sakawdaurn, Suriya-Arunroj Lalitta, Chimngam Motee, Suttisan Nutchanat, Malaivijitnond Suchinda, Mutirangura Apiwat
Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand;
Zoology Program, Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
In Vivo. 2025 Jul-Aug;39(4):1965-1983. doi: 10.21873/invivo.13994.
BACKGROUND/AIM: HMGB1 Box A gene therapy is a promising therapeutic approach for age-associated diseases, based on evidence from and studies in rodents. This study aimed to evaluate long-term safety and musculoskeletal change of the Box A gene in non-human primates.
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.
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 week of the experiment. Box A group trended to gain less weight than the PC group, without experiencing muscle loss.
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.
背景/目的：基于对啮齿动物的研究证据，高迁移率族蛋白B1（HMGB1）A盒基因疗法是一种针对与年龄相关疾病的有前景的治疗方法。本研究旨在评估A盒基因在非人灵长类动物中的长期安全性和肌肉骨骼变化。
对围绝经期猴子每周静脉注射一次对照质粒（PC组）或A盒质粒（A盒组），共注射八周，并观察一年。对两组动物进行安全药理学、血液生化和血液学、骨密度、骨几何学和肌肉密度的评估与比较。
安全药理学测试、一般临床观察以及对中枢神经、心血管和呼吸系统的评估均未发现安全问题。肌肉骨骼系统对A盒的反应表明，PC组和A盒组之间，桡骨和胫骨的骨密度和大小变化呈现相反趋势。A盒减弱了桡骨近端干骺端与年龄相关的骨量增加和骨大小减小。A盒促进了胫骨骨干皮质骨的积累。从实验第48周开始，PC组血糖水平升高，而A盒组未出现此现象。A盒组体重增加趋势低于PC组，且未出现肌肉流失。
本研究表明，在56周的观察期内，A盒是安全的，未引起不良临床症状。值得注意的是，它减轻了与年龄相关的表型，包括改善围绝经期猴子的骨骼健康、降低血糖和减少体重增加。这些结果表明A盒是一种安全的回春药物。
