Long-term Safety Pharmacology and Musculoskeletal Changes of HMGB1 Box A Gene Therapy in Middle-aged Monkeys.

IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
In vivo Pub Date : 2025-07-01 DOI:10.21873/invivo.13994
Sukanya Jaroenporn, Tayanee Chundee, Sakawdaurn Yasom, Lalitta Suriya-Arunroj, Motee Chimngam, Nutchanat Suttisan, Suchinda Malaivijitnond, Apiwat Mutirangura
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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.

中年猴子HMGB1 Box A基因治疗的长期安全性、药理学和肌肉骨骼变化
背景/目的:基于啮齿动物体内和体外研究的证据,HMGB1 Box A基因治疗是一种很有前景的治疗年龄相关疾病的方法。本研究旨在评估Box A基因在非人灵长类动物中的长期安全性和肌肉骨骼变化。材料与方法:围绝经期猕猴静脉注射对照质粒(PC组)或Box a质粒(Box a组),每周1次,连续8周,观察1年。评估和比较各组的安全性药理学、血液生化和血液学、骨密度、骨几何和肌肉密度。结果:安全性药理学试验、一般临床观察以及中枢神经、心血管和呼吸系统的评估显示无安全性问题。骨骼肌系统对Box A的反应表明,PC组和Box A组桡骨和胫骨的骨密度和大小变化方向相反。框A减弱了与年龄相关的桡骨干骺端骨量的增加和骨大小的减少。框A促进胫骨骨干皮质骨蓄积。PC组,而不是Box A组,从实验第48周开始出现血糖水平升高。框A组比PC组增加的体重更少,但没有肌肉损失。结论:在56周的观察期内,本研究表明Box A是安全的,未出现不良临床症状。值得注意的是,它减轻了与年龄相关的表型,包括改善了绝经期猴子的骨骼健康,降低了血糖,减少了体重增加。这些结果表明A是一种安全的返老还童药。
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来源期刊
In vivo
In vivo 医学-医学:研究与实验
CiteScore
4.20
自引率
4.30%
发文量
330
审稿时长
3-8 weeks
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.
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