Comparative evaluation of recombinant human epidermal growth factor and insulin like growth factor-1 coated membranes in the management of isolated millers class 1 gingval recession defects. - NIL

开始日期2024-06-01

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100 项与美卡舍明生物类似药（Chiron Corp）相关的临床结果

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100 项与美卡舍明生物类似药（Chiron Corp）相关的转化医学

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100 项与美卡舍明生物类似药（Chiron Corp）相关的专利（医药）

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135

项与美卡舍明生物类似药（Chiron Corp）相关的文献（医药）

2025-10-01·METABOLISM-CLINICAL AND EXPERIMENTAL

Alteration of IGF-1 bioavailability due to PAPPA2 deficiency leads to sex-specific metabolic disturbances

Article

作者: Chowen, Julie A ; Rivera, Patricia ; Campillo-Calatayud, Ana ; Suárez, Juan ; Del Mar Fernández-Arjona, María ; Barrios, Vicente ; Vera-Fernández, Carlos ; Vargas, Antonio ; Rubio, Leticia ; Rodríguez de Fonseca, Fernando ; Argente, Jesús ; de Ceglia, Marialuisa ; López-Gambero, Antonio J

BACKGROUND:

The growth hormone (GH)/insulin-like growth factor (IGF-1) axis determines optimal growth and affects metabolism and energy homeostasis. Pregnancy-associated plasma protein-A2 (PAPPA2) regulates bioactive IGF-1 availability and patients with PAPPA2 deficiency have impaired growth and glucose metabolism. This axis is altered in metabolic disturbances such as obesity and anorexia nervosa in a sex-specific manner, but the mechanisms involved are not completely understood. Here we evaluated how Pappa2 deficiency affects energy homeostasis, focusing on male and female differences.

METHODS:

Growth and energy homeostasis were determined in male and female Pappa2^ko/ko mice and control Pappa2^wt/wt littermates, as well as their response to recombinant human (rh)PAPPA2, rhIGF-1 and rhIBFBP5. Effects of a high-carbohydrate diet (HCHD) on glucose tolerance, fuel partitioning, de novo lipogenesis and energy homeostasis were determined.

RESULTS:

Pappa2^ko/ko mice had reduced body weight, bone length and lipid deposition associated with higher energy expenditure and intake. Male Pappa2^ko/ko mice had mild glucose intolerance, altered bone mineral properties and higher energy costs for locomotor activity possibly due to inefficient muscle mitochondrial activity; whereas female Pappa2^ko/ko mice had enhanced fatty acid oxidation on a normal diet, but not on a HCHD. All Pappa2^ko/ko mice had lower hepatic fat deposition associated with lower IGF-1 activity in the liver, while fatty acid metabolism dysregulation in adipose tissue was found only in females.

CONCLUSION:

These data reinforce the importance of the GH/IGF-1 axis in metabolic control and emphasize the relevance of its fine-tuned control by Pappa2. Moreover, the differences between sexes in metabolic imbalances underscore the relevance of sex-specific strategies for treatment of metabolic imbalances.

2024-06-01·PROTEIN AND PEPTIDE LETTERS

Comparing the Soluble Form of Recombinant Human Insulin-like Growth Factor-1 (rhIGF-1) in Escherichia coli Using Thioredoxin as Fused and Co-expressed Protein

Article

作者: Tabarzad, Maryam ; Hemmati, Sara ; Ranjbari, Javad ; Maghami, Parvaneh

Introduction::

Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide with various physiological functions. Escherichia coli is one of the most desirable hosts for recombinant protein production, especially for human proteins whose post-translation modifications are not essential for their bioactivity, such as hIGF-1.

Objectives::

In this study, bacterial thioredoxin (Trx) was studied as a fused and non-fused protein to convert the insoluble form of recombinant human IGF-1 (rhIGF-1) to its soluble form in E. coli.

Methods::

The rhIGF-1 was expressed in the E. coli Origami strain in the form of fused-Trx. It was co-expressed with Trx and then purified and quantified. In the next step, the biological activity of rhIGF-1 was evaluated by alkaline phosphatase (ALP) activity assay in human adipose- derived stem cells (hASCs) regarding the differentiation enhancement effect of IGF-1 through the osteogenic process.

Results::

Results showed that Trx in both the fused and non-fused forms had a positive effect on the production of the soluble form of rhIGF-1. A significant increase in ALP activity in hASCs after rhIGF-1 treatment was observed, confirming protein bioactivity.

Conclusion::

It was strongly suggested that the overproduction of Trx could increase the solubility of co-expressed recombinant proteins by changing the redox state in E. coli cells.

2023-12-21·JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry

Article

作者: Bossowski, Artur ; Woelfle, Joachim ; Argente, Jesús ; Perrot, Valerie ; Ramon-Krauel, Marta ; Sert, Caroline ; Maghnie, Mohamad ; Polak, Michel ; Bang, Peter ; Mazain, Sarah

Abstract:

Context:

The European Increlex® Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD).

Objective:

This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1.

Methods:

Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor.

Results:

In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced ≥ 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01.

Conclusion:

Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment.

项与美卡舍明生物类似药（Chiron Corp）相关的新闻（医药）

2025-09-03

·梅斯医学

孩子怎么都长不高......矮小症？甲减？都不是！这类孩子竟“自带防癌体质”！

小浩今年10岁，身高却只有108厘米，比同龄人矮了整整一个头。父母一直担心他是“营养跟不上”或者“甲状腺功能有问题”，带着他跑遍了内分泌科和营养科，甚至尝试过各种补品，但效果甚微。在医院的详细评估中，医生发现小浩的智力和日常发育都很正常，但骨龄明显落后。实验室检查显示，他的血清生长激素水平并不低，甚至偏高，但类胰岛素生长因子-1（IGF-1）水平却极低。进一步的基因检测揭示了真相：小浩的生长激素受体（GHR）基因发生突变，导致体内虽然有充足的生长激素，却无法作用于组织产生正常的生长反应。这就是罕见的莱伦综合征（Laron syndrome），又被称为生长激素不敏感综合征。医生解释，这类患儿由于缺乏对生长激素的敏感性，传统的生长激素治疗无效，目前主要依赖 IGF-1 替代治疗来改善生长。概述莱伦综合征（Laron syndrome），又称原发性生长激素不敏感综合征（primary growth hormone insensitivity syndrome，GHIS），是一类罕见的导致身材矮小、代谢异常等临床表现的常染色体隐性遗传病，由于生长激素受体（growthhormone receptor，GHR）或受体后信号通路上相关基因突变所致。症状Laron综合征是一种由于生长激素受体缺陷引起的遗传性疾病。患者出生时体重大多正常，但身长较短，随着生长速度减缓，身高通常低于正常水平。男性患者终身身高116-142cm，女性为108-136cm。患者的手、足和内脏器官较小，且可能伴有髋关节脱位、主动脉瓣狭窄、隐睾等畸形。面容方面，患者通常表现为前额突出、鞍鼻、小下颌，头围偏小，且头发稀疏。部分患者有“落日征”，地中海和中东地区的患者可能出现蓝巩膜。出牙延迟，乳牙多发龋齿，下颌骨小，牙列不齐。骨骼肌肉方面，部分患者可能有髋关节脱位、股骨头坏死，且发音尖细。85%的患者肘关节活动受限。代谢方面，患者可能有低血糖和肥胖，且常伴有高脂血症。性发育上，男性生殖器较小，青春发育延迟，但最终性功能和生育能力正常。Laron综合征的一个特点是肿瘤发生率低于普通人群。诊断如果患者存在严重生长障碍，骨龄落后、循环中生长激素水平正常或升高，同时伴有IGF-1和IGFBP-3水平较低，则应怀疑存在Laron综合征，结合IGF-1生成试验的结果初步得到临床诊断。根据1994年Blum等人提出的改良的Laron综合征评分系统，评分≥5分则支持Laron综合征的诊断（表2），最终确诊需要进行候选基因测序。治疗Laron综合征患者通常对生长激素（rhGH）治疗无反应，因此重组人胰岛素生长因子-1（rhIGF-1）成为唯一有效的治疗药物。rhIGF-1自1986年首次合成以来，经过多年的研究与临床应用，证明了其显著的治疗效果。在一项针对76名生长激素不敏感患者的研究中，rhIGF-1治疗持续了12年，治疗剂量为60～120μg/kg，每日2次。研究显示，第一年治疗中，患者的生长速度从2.8cm/年增加到8.0cm/年。尽管随后的治疗生长速度有所下降，但仍高于基线水平。最常见的不良反应包括低血糖（发生率49%），注射部位脂肪增生（32%）以及扁桃体/腺样体肥大（22%）。有学者认为，单独使用rhIGF-1可能对垂体分泌的生长激素（GH）产生负反馈作用。然而，rhIGF-1不仅可以增强GH的生长促进作用，还能维持IGFBP和ALS的正常水平，调节GH的抗胰岛素作用，从而改善胰岛素抵抗状态。因此，联合使用rhGH和rhIGF-1有望提高治疗效果。尽管如此，联合治疗方案仍处于研究阶段，其安全性和有效性需要进一步评估。参考资料：[1] Laron Z. Lessons From 50 Years Of Study OfLaron Syndrome. Endocrine practice: official journal of the American College ofEndocrinology and the American Association of ClinicalEndocrinologists,2015,21(12): 1395-1402.[2] Laron Z, Kauli R. Fifty seven years offollow-up of the Israeli cohort of Laron Syndrome patients-From discovery totreatment. Growth hormone & IGF research : official journal of the GrowthHormone Research Society and the International IGF Research Society, 2016,28:53-56.[3] Rosenfeld RG. The IGF system: new developmentsrelevant to pediatric practice. Endocrine development, 2005, 9:1-10.来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！

临床结果临床研究

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