Last update 01 Nov 2024

GM2AP1

Last update 01 Nov 2024

Basic Info

Synonyms

GM2 ganglioside activator pseudogene 1, GM2AP, GM2AP1

Introduction-

Drugs associated with GM2AP1

AL-801

Target

GM2AP1

Mechanism

GM2A inhibitors

Active Org.

Alps Biotech Co., LTDStartup

Originator Org.

Alps Biotech Co., LTDStartup

Active Indication

Lung Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GM2AP1

100 Translational Medicine associated with GM2AP1

0 Patents (Medical) associated with GM2AP1

Literatures (Medical) associated with GM2AP1

01 Nov 2024·Toxicology

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats

Article

Author: Blanco-Gozalo, Víctor ; López-Hernández, Francisco J ; Sancho-Martínez, Sandra M ; Quiros, Yaremi ; Vicente-Vicente, Laura ; Casanova, Alfredo G

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

24 May 2023·International journal of molecular sciences

Biochemical Correction of GM2 Ganglioside Accumulation in AB-Variant GM2 Gangliosidosis.

Article

Author: Deschenes, Natalie M ; Sangrar, Waheed ; Cheng, Camilyn ; Ryckman, Alex E ; Quinville, Brianna M ; Mitchell, Melissa ; Khanal, Prem ; Gray, Steven J ; Walia, Jagdeep S ; Chen, Zhilin

GM2 gangliosidosis is a group of genetic disorders that result in the accumulation of GM2 ganglioside (GM2) in brain cells, leading to progressive central nervous system (CNS) atrophy and premature death in patients. AB-variant GM2 gangliosidosis (ABGM2) arises from loss-of-function mutations in the GM2 activator protein (GM2AP), which is essential for the breakdown of GM2 in a key catabolic pathway required for CNS lipid homeostasis. In this study, we show that intrathecal delivery of self-complementary adeno-associated virus serotype-9 (scAAV9) harbouring a functional human GM2A transgene (scAAV9.hGM2A) can prevent GM2 accumulation in in GM2AP-deficient mice (Gm2a^-/- mice). Additionally, scAAV9.hGM2A efficiently distributes to all tested regions of the CNS within 14 weeks post-injection and remains detectable for the lifespan of these animals (up to 104 weeks). Remarkably, GM2AP expression from the transgene scales with increasing doses of scAAV9.hGM2A (0.5, 1.0 and 2.0 × 10¹¹ vector genomes (vg) per mouse), and this correlates with dose-dependent correction of GM2 accumulation in the brain. No severe adverse events were observed, and comorbidities in treated mice were comparable to those in disease-free cohorts. Lastly, all doses yielded corrective outcomes. These data indicate that scAAV9.hGM2A treatment is relatively non-toxic and tolerable, and biochemically corrects GM2 accumulation in the CNS-the main cause of morbidity and mortality in patients with ABGM2. Importantly, these results constitute proof-of-principle for treating ABGM2 with scAAV9.hGM2A by means of a single intrathecal administration and establish a foundation for future preclinical research.

01 Feb 2023·Molecular Genetics and Metabolism

Plasma GM2 ganglioside potential biomarker for diagnosis, prognosis and disease monitoring of GM2-Gangliosidosis

Article

Author: Khrouf, Walid ; Schlemmer, Dimitri ; Turki, Ilhem Ben Youssef ; Lamari, Foudil ; Ganne, Benjamin ; Marcelino, Chloé ; Dauriat, Benjamin ; Blondel, Amélie ; Fernández-Eulate, Gorka ; Kraoua, Ichraf ; Caillaud, Catherine ; Bonnefont-Rousselot, Dominique ; Nadjar, Yann

GM2-Gangliosidosis are a group of inherited lysosomal storage pathologies characterized by a large accumulation of G_M2 ganglioside in the lysosome. They are caused by mutation in HEXA or HEXB causing reduced or absent activity of a lysosomal β-hexosaminidase A, or mutation in GM2A causing defect in GM2 activator protein (GM2AP), an essential protein for the activity of the enzyme. Biochemical diagnosis relies on the measurement of β-hexosaminidases A and B activities, which is able to detect lysosomal enzyme deficiency but fails to identify defects in GM2AP. We developed a rapid, specific and sensitive liquid chromatography-mass spectrometry-based method to measure simultaneously G_M1, G_M2, G_M3 and G_D3 molecular species. Gangliosides were analysed in plasma from 19 patients with GM2-Gangliosidosis: Tay-Sachs (n = 9), Sandhoff (n = 9) and AB variant of GM2-Gangliosidosis (n = 1) and compared to 20 age-matched controls. Among patients, 12 have a late adult-juvenile-onset and 7 have an infantile early-onset of the disease. Plasma G_M2 molecular species were increased in all GM2-Gangliosidosis patients (19/19), including the patient with GM2A mutation, compared to control individuals and compared to patients with different other lysosomal storage diseases. G_M234:1 and G_M234:1/G_M334:1 ratio discriminated patients from controls with 100% sensitivity and specificity. G_M234:1 and G_M234:1/G_M334:1 were higher in patients with early-onset compared to those with late-onset of the disease, suggesting a relationship with severity. Longitudinal analysis in one adult with Tay-Sachs disease over 9 years showed a positive correlation of G_M234:1 and G_M234:1/G_M334:1 ratio with age at sampling. We propose that plasma G_M2 34:1 and its ratio to G_M3 34:1 could be sensitive and specific biochemical diagnostic biomarkers for GM2-Gangliosidosis including AB variant and could be useful as a first line diagnostic test and potential biomarkers for monitoring upcoming therapeutic efficacy.

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GM2AP1

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