Evaluation of the Re-mineralizing Effect of Biomimetic Self-Assembling Peptides in Post Orthodontic White Spot Lesions Compared to Fluoride-Based Delivery Systems

During re-mineralization of white spot lesion, Will biomimetic self-assembling peptides improve the re-mineralizating effect of the post orthodontic white spot lesion compared to fluoride-based delivery systems?

开始日期2019-05-01

申办/合作机构

Cairo University

NCT02204397 / Completed临床2期IIT

A Single-center, Open-Label, Exploratory Study to Assess the Tolerability and Safety of the Addition of Ustekinumab to INGAP Peptide for 12 Weeks in Adult Patients With Type 1 Diabetes Mellitus

A proof-of-concept for safety and preliminary clinical efficacy of a combined regimen of INGAP-P for β-cell regeneration and ustekinumab for IL-12-23 autoimmune modulation in patients with established T1DM.

开始日期2015-11-01

申办/合作机构

The Jewish General Hospital

NCT00995540 / Terminated临床2期

A Multiple-center, Randomized, Double-blind, Placebo-controlled, Parallel Study to Assess the Tolerability, Safety, and Efficacy of INGAP Peptide Given Subcutaneously as Injections t.i.d. for 12 Weeks in Adult Patients With Type 1 Diabetes Mellitus

INGAP Peptide acetate is the active ingredient of INGAP Peptide Solution for Injection. It is being developed as an antidiabetic agent for the restoration of endogenous insulin secretion in patients with type 1 diabetes mellitus (T1DM) and in insulin-deficient patients with type 2 diabetes mellitus (T2DM). This clinical study is designed to generate additional data regarding the appropriate dose and dosing regimen and to evaluate safety and efficacy in patients with T1DM.

开始日期2009-11-01

申办/合作机构

Exsulin Corp.

100 项与 INGAP Peptide(Eastern Virginia Medical School) 相关的临床结果

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100 项与 INGAP Peptide(Eastern Virginia Medical School) 相关的转化医学

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项与 INGAP Peptide(Eastern Virginia Medical School) 相关的文献（医药）

2024-08-15·Heliyon

Characterization of MSCs expressing islet neogenesis associated protein (INGAP): INGAP secretion and cell survival in vitro and in vivo.

Article

作者: Eliopoulos, Nicoletta ; Rosenberg, Lawrence ; Assouline-Thomas, Beatrice ; Zhao, Jing ; Petropavlovskaia, Maria ; Cuerquis, Jessica ; Violette-Deslauriers, Shaun ; Nano, Eni

Mesenchymal stem/stromal cells (MSCs) are emerging as a new therapy for diabetes. Here we investigate the properties of MSCs engineered to express Islet Neogenesis Associated Protein (INGAP) previously shown to reverse diabetes in animal models and evaluate their potential for anti-diabetic applications in mice. Mouse bone marrow-derived MSCs retrovirally transduced to co-express INGAP, Firefly Luciferase and EGFP (INGAP-MSCs), were characterized in vitro and implanted intraperitoneally (IP) into non-diabetic and diabetic C57BL/6 mice (Streptozotocin model) and tracked by live bioluminescence imaging (BLI). Distribution and survival of IP injected INGAP-MSCs differed between diabetic and non-diabetic mice, with a rapid clearance of cells in the latter, and a stronger retention (up to 4 weeks) in diabetic mice concurring with homing towards the pancreas. Interestingly, INGAP-MSCs inhibited the progression of hyperglycemia starting at day 3 and lasting for the entire 6 weeks of the study. Pursuing greater retention, we investigated the survival of INGAP-MSCs in hydrogel matrices. When mixed with Matrigel™ and injected subcutaneously into non-diabetic mice, INGAP-MSCs remained in the implant up to 16 weeks. In vitro tests in three matrices (Matrigel™, Type I Collagen and VitroGel®-MSC) demonstrated that INGAP-MSCs survive and secrete INGAP, with best results at the density of 1-2 x 10⁶ cells/mL. However, all matrices induced spontaneous adipogenic differentiation of INGAP-MSCs in vitro and in vivo, which requires further investigation of its potential impact on MSC therapeutic properties. In summary, based on their ability to stop the rise in hyperglycemia in STZ-treated mice, INGAP-MSCs are a promising therapeutic tool against diabetes but require further research to improve cell delivery and survival.

2024-03-01·Peptides

Structural modifications of INGAP-PP present in HTD4010 peptide potentiate its effect on rat islet gene expression and insulin secretion.

Article

作者: Flores, Luis E ; Gagliardino, Juan J ; Román, Carolina L ; Maiztegui, Bárbara ; Algañarás, Macarena

Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and altered insulin secretion due to a progressive loss of β-cell mass and function. Today, most antidiabetic agents are designed to resolve impaired insulin secretion and/or insulin resistance, and only GLP-1-based formulations contribute to stopping the decline in β-cell mass. HTD4010, a peptide carrying two modifications of the amino acid sequence of INGAP-PP (N-terminus acetylation and substitution of Asn13 by Ala) showed greater plasma stability and could be a good candidate for proposal as a drug that could improve β cell mass and function lost in T2D. In the present study, we showed that HTD4010 included in the culture media of normal rat islets at a dose 100 times lower than that used for INGAP-PP was able to modulate, in the same way as the original peptide, both insulin secretion in response to glucose and the expression of key genes related to insular function, insulin and leptin intracellular pathways, neogenesis, apoptosis, and inflammatory response. Our results confirm the positive effect of HTD4010 on β-cell function and gene expression of factors involved in the maintenance of β-cell mass. Although new assays in animal models of prediabetes and T2D must be performed to be conclusive, our results are very encouraging, and they suggest that the use of HTD4010 at a dose 100 times lower than that of INGAP-PP could minimize its side effects in a future clinical trial.

2023-01-01·Frontiers in endocrinology

Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs.

Article

作者: Román, Carolina L ; Nazer, Ezequiel ; Flores, Luis E ; Rodríguez-Seguí, Santiago A ; Maiztegui, Bárbara ; Romero, Agustín ; Gagliardino, Juan J ; Heidenreich, Ana C ; Algañarás, Macarena

BackgroundDiabetes mellitus is characterized by chronic hyperglycemia with loss of β-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce β-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets.Methods and findingsRat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1β, IL1β+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1β and vitamin D in β-cells. These include Ri-lnc1, which is enriched in mature β-cells.ConclusionsOur results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on β-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic β-cells and downregulated by IL1β treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in β-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.

100 项与 INGAP Peptide(Eastern Virginia Medical School) 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
1型致死性发育不良	临床2期	加拿大	The Jewish General Hospital	2015-11-01
1型糖尿病	临床2期	美国	GMP Endotherapeutics Inc	2001-12-01
1型糖尿病	临床2期	美国	GMP Endotherapeutics Inc	2001-12-01
2型糖尿病	临床2期	-	The Jewish General Hospital	-
2型糖尿病	临床2期	-	Eastern Virginia Medical School	-
2型糖尿病	临床2期	-	McGill-Queen's University Press	-