The purpose of this study is to determine the safety and efficacy of a PEPIDH1M vaccine in combination with vorasidenib, a dual inhibitor of mutant IDH1 and IDH2 enzymes, in adult patients diagnosed with recurrent IDH1 mutant lower grade gliomas.

Start Date01 Jan 2025

Sponsor / Collaborator

Duke University

[+1]

NCT02771301 / Unknown statusNot ApplicableIIT

Safety and Efficacy of IDH1R132H-DC Vaccine in Gliomas

This trial is aimed at evaluating the safety and efficacy of IDH1R132H-DC vaccine in glioma with IDH1R132H mutation.

Start Date01 Feb 2016

Sponsor / Collaborator

Hebei Yanda Hospital

[+1]

NCT02193347 / CompletedPhase 1IIT

Patients With IDH1 Positive Recurrent Grade II Glioma Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine

Potential subjects with progressive Grade II primary brain tumor that have IDH1 positive testing from the primary tumor (initial diagnosis) will be offered this treatment study in order to test the safety of the PEPIDH1M vaccine in combination with standard chemotherapy (temozolomide).

Start Date28 Jan 2016

Sponsor / Collaborator

Duke University

100 Clinical Results associated with IDH1 R132H

100 Translational Medicine associated with IDH1 R132H

0 Patents (Medical) associated with IDH1 R132H

106

Literatures (Medical) associated with IDH1 R132H

01 Nov 2024·Pathology - Research and Practice

Clinical utility of plasma cell-free DNA (cfDNA) in diffuse gliomas for the detection of IDH1 R132H mutation

Article

Author: Mohan, Trishala ; Bora, Santanu Kumar ; Sarkar, Chitra ; Suri, Ashish ; Suri, Vaishali ; Sharma, Mehar Chand ; Singh, Swati ; Singh, Jyotsna ; Faruq, Mohammed ; Dandapath, Iman ; Bhardwaj, Supriya ; Kedia, Shweta ; Das, Sumanta

Liquid biopsy for CNS tumors is in its nascent phase, hindered by the low levels of circulating tumor DNA (ctDNA). Overcoming this challenge requires highly sensitive molecular techniques. DD-PCR emerges as a standout technique due to its ability to identify rare mutations, copy number variations, and circulating nucleic acids, making it one of the best methods for identifying somatic mutations in cell-free DNA (cfDNA). Despite promising results from various studies demonstrating the feasibility of obtaining informative ctDNA profiles from liquid biopsy samples, challenges persist, including the need to standardize sample collection, storage, and processing methods, define clear assay positivity thresholds, and address the overall low assay sensitivity. Our two-phase study began by assessing DD-PCR efficacy in FFPE tissues, revealing robust concordance with immunohistochemistry. In Phase 1 (85 cases), DD-PCR on FFPE tissues demonstrated 100 % sensitivity and specificity for IDH1 R132H mutations. In Phase 2 (100 cases), analysis extended to cfDNA, maintaining high specificity (100 %) with moderate sensitivity (44.2 %). Overall concordance with immunohistochemistry was 61 %, highlighting liquid biopsy's potential in glioma management. The findings emphasized DD-PCR's clinical utility in both tissue and liquid biopsy, underscoring its role in early detection, diagnosis, and therapeutic monitoring of diffuse gliomas.

15 Oct 2024·Biochemistry

Gaining Insight into the Catalytic Mechanism of the R132H IDH1 Mutant: A Synergistic DFT Cluster and Experimental Investigation

Article

Author: Nguyen, Nguyen P. ; Broome, Joshua A. ; Baumung, Cassidy R. E. ; Chen, Vincent C. ; Bushnell, Eric A. C.

Human isocitrate dehydrogenase 1 (IDH1) is an enzyme that is found in humans that plays a critical role in aerobic metabolism. As a part of the citric acid cycle, IDH1 becomes responsible for catalyzing the oxidative decarboxylation of isocitrate to form α-ketoglutarate (αKG), with nicotinamide adenine dinucleotide phosphate (NADP⁺) as a cofactor. Strikingly, mutations of the IDH1 enzyme have been discovered in several cancers including glioblastoma multiforme (GBM), a highly aggressive form of brain cancer. It has been experimentally determined that single-residue IDH1 mutations occur at a very high frequency in GBM. Specifically, the IDH1 R132H mutation is known to produce (D)2-hydroxyglutarate (2HG), a recognized oncometabolite. Using the previously determined catalytic mechanism of IDH1, a DFT QM model was developed to study the mechanistic properties of IDH1 R132H compared to wild type enzyme. Validating these insights, biochemical in vitro assays of metabolites produced by mutant vs wild type enzymes were measured and compared. From the results discussed herein, we discuss the mechanistic impact of mutations in IDH1 on its ability to catalyze the formation of αKG and 2HG.

10 Sep 2024·Acta neuropathologica communications

A patient-derived cell model for malignant transformation in IDH-mutant glioma.

Article

Author: Tran, Bao ; Brender, Jeffrey R ; Kishimoto, Shun ; Wei, Jun S ; Lu, Peng ; Yu, Guangyang ; Song, Hua ; Kim, Olga ; Andresson, Thorkell ; Zhang, Wei ; Li, Qi ; Abdullaev, Zied ; Wu, Jing ; Yamamoto, Kazutoshi ; Krishna, Murali C ; Quezado, Martha ; Wu, Xiaolin ; Blackman, Burchelle ; Sergi, Zach ; Crooks, Danel R ; Zhang, Meili ; Khan, Javed

Malignant transformation (MT) is commonly seen in IDH-mutant gliomas. There has been a growing research interest in revealing its underlying mechanisms and intervening prior to MT at the early stages of the transforming process. Here we established a unique pair of matched 3D cell models: 403L, derived from a low-grade glioma (LGG), and 403H, derived from a high-grade glioma (HGG), by utilizing IDH-mutant astrocytoma samples from the same patient when the tumor was diagnosed as WHO grade 2 (tumor mutational burden (TMB) of 3.96/Mb) and later as grade 4 (TMB of 70.07/Mb), respectively. Both cell models were authenticated to a patient's sample retaining endogenous expression of IDH1 R132H. DNA methylation profiles of the parental tumors referred to LGG and HGG IDH-mutant glioma clusters. The immunopositivity of SOX2, NESTIN, GFAP, OLIG2, and beta 3-Tubulin suggested the multilineage potential of both models. 403H was more prompt to cell invasion and developed infiltrative HGG in vivo. The differentially expressed genes (DEGs) from the RNA sequencing analysis revealed the tumor invasion and aggressiveness related genes exclusively upregulated in the 403H model. Pathway analysis showcased an enrichment of genes associated with epithelial-mesenchymal transition (EMT) and Notch signaling pathways in 403H and 403L, respectively. Mass spectrometry-based targeted metabolomics and hyperpolarized (HP) 1-¹³C pyruvate in-cell NMR analyses demonstrated significant alterations in the TCA cycle and fatty acid metabolism. Citrate, glutamine, and 2-HG levels were significantly higher in 403H. To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

IDH1 R132H

Basic Info

Related

Analysis