An Open-Label, Sequential, Dose Escalation Study of the Pharmacokinetics, Safety, and Preliminary Efficacy of MDT-15 in Subjects With Lumbosacral Radiculopathy

The primary objectives of this clinical trial are to investigate the pharmacokinetics and safety of MDT-15 pellets in escalating sequential doses administered to different cohorts. Preliminary efficacy data will also be collected for assessment.

开始日期2013-07-01

申办/合作机构

Medtronic Spinal & Biologics Europe

100 项与 MDT-15 相关的临床结果

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100 项与 MDT-15 相关的转化医学

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100 项与 MDT-15 相关的专利（医药）

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项与 MDT-15 相关的文献（医药）

2020-07-01·Biochemical and Biophysical Research Communications

Lipid metabolic sensors of MDT-15 and SBP-1 regulated the response to simulated microgravity in the intestine of Caenorhabditis elegans

Article

作者: Liu, Huanliang ; Sun, Lingmei ; Zhang, Ruijie ; Wang, Dayong ; Li, Dan

Caenorhabditis elegans is a useful animal model to determine the underlying mechanism for the response to simulated microgravity. In this study, we employed C. elegans as an animal model to investigate the role of lipid metabolic sensors in regulating the response to simulated microgravity. Among the lipid metabolic sensors, simulated microgravity treatment could increase the expressions of sbp-1 and mdt-15. RNAi knockdown of sbp-1 or mdt-15 induced a susceptibility to toxicity of simulated microgravity, suggesting the alteration in SBP-1 and MDT-1 mediated a protective response to simulated microgravity. Tissue-specific activity analysis demonstrated that both MDT-15 and SBP-1 could act in the intestine to regulate the response to simulated microgravity. Genetic interaction analysis further indicated that intestinal MDT-15 acted upstream of SBP-1 to regulate the response to simulated microgravity. During the control of response to simulated microgravity, fatty acyl CoA desaturase FAT-6 was identified as the downstream target of intestinal SBP-1. Therefore, the identified signaling cascade of MDT-15-SBP-1-FAT-6 suggested the important function of lipid metabolic sensors in mediating a novel intestinal signaling pathway to regulate the response to simulated microgravity in nematodes.

2020-01-01·Environmental Pollution

Lipid metabolic response to polystyrene particles in nematode Caenorhabditis elegans

Article

作者: Wang, Dayong ; Wu, Qiuli ; Yang, Yunhan ; Shao, Huimin

Nanoplastics can be used in various fields, such as personal care products. Nevertheless, the effect of nanoplastic exposure on metabolism and its association with stress response remain largely unclear. Using Caenorhabditis elegans as an animal model, we determined the effect of nanopolystyrene exposure on lipid metabolism and its association with the response to nanopolystyrene. Exposure (from L1-larave to adult day-3) to 100 nm nanopolystyrene (≥1 μg/L) induced severe lipid accumulation and increase in expressions of mdt-15 and sbp-1 encoding two lipid metabolic sensors. Meanwhile, we found that SBP-1 acted downstream of intestinal MDT-15 during the control of response to nanopolystyrene. Intestinal transcriptional factor SBP-1 activated two downstream targets, fatty acyl CoA desaturase FAT-6 and heat-shock protein HSP-4 (a marker of endoplasmic reticulum unfolded protein response (ER UPR)) to regulate nanopolystyrene toxicity. Both MDT-15 and SBP-1 were involved in the activation of ER-UPR in nanopolystyrene exposed nematodes. Moreover, SBP-1 regulated the innate immune response by activating FAT-6 in nanopolystyrene exposed nematodes. In the intestine, function of MDT-15 and SBP-1 in regulating nanopolystyrene toxicity was under the control of upstream signaling cascade (PMK-1-SKN-1) in p38 MAPK signaling pathway. Therefore, our data raised an important molecular basis for potential protective function of lipid metabolic response in nanopolystyrene exposed nematodes.

2019-09-01·Pharmacological Research2区 · 医学

Citrus aurantium L. var. amara Engl. inhibited lipid accumulation in 3T3-L1 cells and Caenorhabditis elegans and prevented obesity in high-fat diet-fed mice

2区 · 医学

Article

作者: Wan, Lin ; Wang, Tian-Xing ; Shen, Chun-Yan ; Jiang, Jian-Guo

Natural products with anti-obesity effects and few side effects have attracted great attention recently. Citrus aurantium L. var. amara Engl. (CAVA) is popularly consumed as an edible and medicinal resource in China. However, its anti-obesity effects were poorly understood. The anti-obesity effects of CAVA extracts were systematically evaluated using 3T3-L1 cells, Caenorhabditis elegans (C. elegans) and high fat diet (HFD)-fed mice. Flavonoid-rich (EA) extracts with neohesperidin, hesperidin and naringin comprising 32.15%, were isolated from CAVA. EA extracts treatment significantly inhibited differentiation of 3T3-L1 preadipocytes by modulating lipid metabolism-related mediators. EA extracts supplementation also inhibited antioxidant responses in C. elegans by decreasing reactive oxygen species generation and malonaldehyde value, and increasing superoxide dismutase content. EA extracts feeding markedly decreased triglyceride (TG) content, and affected expression of genes involved in lipid and glucose metabolism in wild type C. elegans. TG content in mdt-15 (XA7702) mutants was not decreased by EA extracts administration, suggesting that EA extracts treatment might inhibit lipid accumulation in C. elegans dependent on mdt-15. EA extracts intervention further reduced body weight gain and modulated plasma biochemical parameters in HFD-fed mice. EA extracts treatment prevented HFD-induced epididymal adipose hypertrophy, liver oxidative injuries and steatosis. EA extracts administration also strongly prevented HFD-induced reduction of gut microbial diversity, decreased the Firmicutes-to-Bacteroidetes ratio and the Erysipelotrichaceae abundance, and enhanced the Biﬁdobacteriace abundance in HFD-fed mice. EA extracts from blossoms of CAVA were excellent antiobesogenic candidates that acted through multiple mechanisms that acted simultaneously.

100 项与 MDT-15 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
腰骶神经根病变	临床2期	美国	Medtronic Spinal & Biologics Europe	2013-07-01
坐骨神经痛	临床2期	美国	Medtronic Spinal & Biologics Europe	2013-07-01