Bellagamba Olivia, Guo Aaron J, Senthilkumar Sandhya, Lillevik Synneva Hagen, De Biase Davide, Lai Kent, Balakrishnan Bijina
Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Denver, Colorado, USA.
J Inherit Metab Dis. 2025 Mar;48(2):e70002. doi: 10.1002/jimd.70002.
Classic galactosemia (CG) is a rare inherited metabolic disease caused by mutations in the GALT gene encoding the enzyme galactose-1 phosphate uridylyltransferase in galactose metabolism. The condition develops as a potentially fatal illness during the newborn period, but its acute clinical manifestations can be alleviated through a galactose restricted diet. Nonetheless, such dietary intervention is inadequate in preventing significant long-term consequences, including neurological impairments, growth restriction, cognitive delays, and, for most females, primary ovarian insufficiency. At present, no effective therapy exists to stop the progression of these complications, highlighting the urgent need for new treatment approaches to be developed. Supplements have been used in the treatment of other inborn errors of metabolism; however, they are not typically included in the clinical therapeutic regimen for CG. Recently, our research team has demonstrated that two generally recognized as safe supplements (purple weet potato color, PSPC and myo-inositol, MI) have been effective in partially restoring functions in the ovaries of our GalT-KO mouse model. However, the toxicological profile of both PSPC and MI has not been determined. In this study, we investigated the acute (30 days) and chronic (180 days) oral toxicities of PSPC and MI both in WT control and GalT-KO mice. Furthermore, our study aims to evaluate the effectiveness of oral feeding of PSPC and MI in correcting motor-related and behavioral phenotypes in GalT-KO mice. The long-term treatment of MI at a lower dose demonstrated promising improvements in motor deficit and anxiety driven hyperactivity in the mutant mice.
经典型半乳糖血症(CG)是一种罕见的遗传性代谢疾病,由编码半乳糖代谢中1-磷酸半乳糖尿苷酰转移酶的GALT基因突变引起。该病在新生儿期会发展为一种潜在致命疾病,但其急性临床表现可通过限制半乳糖饮食得到缓解。尽管如此,这种饮食干预在预防重大长期后果方面并不充分,这些后果包括神经损伤、生长受限、认知延迟,以及对大多数女性而言的原发性卵巢功能不全。目前,尚无有效的治疗方法来阻止这些并发症的进展,这凸显了开发新治疗方法的迫切需求。补充剂已被用于治疗其他先天性代谢缺陷;然而,它们通常不包括在CG的临床治疗方案中。最近,我们的研究团队证明,两种普遍认为安全的补充剂(紫薯色素,PSPC和肌醇,MI)在部分恢复我们的GalT-KO小鼠模型卵巢功能方面是有效的。然而,PSPC和MI的毒理学特征尚未确定。在本研究中,我们调查了PSPC和MI在野生型对照小鼠和GalT-KO小鼠中的急性(30天)和慢性(180天)经口毒性。此外,我们的研究旨在评估经口喂食PSPC和MI对纠正GalT-KO小鼠运动相关和行为表型的有效性。较低剂量的MI长期治疗显示,突变小鼠的运动缺陷和焦虑驱动的多动有了有希望的改善。