Delving into the Latest Updates on N-acetyl-D-mannosamine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-Actamido-2-deoxy-D-mannose, D-ManNAc, LB-301 - Leadiant Biosciences

+ [7]

Target-

Mechanism

Glycosylation stimulants, Proteins modulators

Therapeutic Areas

Nervous System DiseasesCongenital DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication

Distal MyopathiesDistal Myopathy, Nonaka Type

Inactive Indication

Kidney Diseases

Originator Organization

National Institutes of Health

Active Organization

Leadiant Biosciences, Inc.

National Institutes of Health

Inactive Organization

National Human Genome Research Institute

National Institute of Diabetes & Digestive & Kidney Diseases

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

Structure

Molecular FormulaC8H15NO6

InChIKeyMBLBDJOUHNCFQT-WCTZXXKLSA-N

CAS Registry3615-17-6

GNE myopathy is a rare genetic muscle disease characterized by progressive muscle atrophy and weakness. The disease is caused by mutations in the gene that encodes the enzyme that initiates and regulates N-acetylneuraminic acid (Neu5Ac) biosynthesis and glycan sialylation. Currently, there is no therapy available for this disease. N-Acetylmannosamine (ManNAc), an orphan drug in development for GNE myopathy, is an uncharged monosaccharide and the first committed precursor in Neu5Ac biosynthesis. In this randomized, double-blind, placebo-controlled trial the efficacy and long-term safety of ManNAc will be evaluated in subjects with GNE myopathy.

Start Date05 Apr 2022

Sponsor / Collaborator

Leadiant Biosciences, Inc.

[+4]

100 Clinical Results associated with N-acetyl-D-mannosamine

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100 Translational Medicine associated with N-acetyl-D-mannosamine

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100 Patents (Medical) associated with N-acetyl-D-mannosamine

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144

Literatures (Medical) associated with N-acetyl-D-mannosamine

01 Jan 2024·Journal of chromatography. A

Surface multi-walled carbon nanotube modified quaternary amine-functionalized polymers for purification and determination of glyphosate and its four metabolites in plasma samples

Article

Author: Yan, Peng ; Ye, Meijun ; Guo, Yanbo ; He, Qian ; Pan, Shengdong ; Zhang, Dandan

The present study focused on the pretreatment and detection of GLY and its four metabolites AMPA, N-acetyl AMPA, N-methyl GLY and N-acetyl GLY in plasma samples. Multi-walled carbon nanotube-modified quaternary amine-functionalized polymers (QA-PDNV@MWCNTs) were synthesized in a controlled manner by self-assembly, and its morphology and composition were extensively characterized. The QA-PDNV@MWCNTs microspheres were then used as an SPE adsorbent for the preparation and rapid determination of GLY and its four metabolites in plasma samples combined with ultra-performance liquid chromatography-high resolution mass spectrometry (UPLCHRMS). The SPE conditions based on QA-PDNV@MWCNTs were optimized for GLY and its metabolites to obtain the best purification efficiency. The experimental results show that when the adsorbent contains 8% MWCNTs, it can balance the adsorption of target analytes and the purification performance of the adsorbent for impurities. In addition, this study compared the QA-PDNV@MWCNTs based SPE method with the commercial Waters Oasis MAX SPE cartridge and the results showed that the developed method in this study has better resistance to matrix interference. Under optimal conditions, the recoveries of GLY and its metabolites spiked in plasma were 82.6-99.4 % with relative standard deviations (RSDs) of 1.0-7.8 %. The limits of detection (LODs, S/N ≥ 3) and limits of quantification (LOQs, S/N ≥ 9) of the method were 0.05-0.33 μg/L and 0.15-1.00 μg/L, respectively. Finally, the developed QA-PDNV@MWCNTs based SPE-UPLCHRMS method was used to confirm GLY poisoning not only on the basis of the detection of the GLY prototype, but also on the basis of its four metabolites.

24 Nov 2023·Frontiers in bioscience (Landmark edition)

Evaluation of N-Acetylmannosamine Administration to Restore Sialylation in GNE-Deficient Human Embryonal Kidney Cells

Article

Author: Selke, Philipp ; Horstkorte, Rüdiger ; Bork, Kaya ; Peters, Emilia ; Gesper, Astrid

BACKGROUND:

A key mechanism in the neuromuscular disease GNE myopathy (GNEM) is believed to be that point mutations in the GNE gene impair sialic acid synthesis - maybe due to UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) activity restrictions - and resulting in muscle tissue loss. N-acetylmannosamine (ManNAc) is the first product of the bifunctional GNE enzyme and can therefore be regarded as a precursor of sialic acids. This study investigates whether this is also a suitable substance for restoring the sialic acid content in GNE-deficient cells.

METHODS:

A HEK-293 GNE-knockout cell line was generated using CRISPR-Cas9 and analyzed for its ability to synthesize sialic acids. The cells were then supplemented with ManNAc to compensate for possible GNE inactivity and thereby restore sialic acid synthesis. Sialic acid levels were monitored by immunoblot and high performance liquid chromatography (HPLC).

RESULTS:

The HEK-293 GNE-knockout cells showed almost no polysialylation signal (immunoblot) and a reduced overall (-71%) N-acetylneuraminic acid (Neu5Ac) level (HPLC) relative to total protein and normalized to wild type level. Supplementation of GNE-deficient HEK-293 cells with 2 mM ManNAc can restore polysialylation and free intracellular sialic acid levels to wild type levels. The addition of 1 mM ManNAc is sufficient to restore the membrane-bound sialic acid level.

CONCLUSIONS:

Although the mechanism behind this needs further investigation and although it remains unclear why adding ManNAc to GNE-deficient cells is sufficient to elevate polysialylation back to wild type levels - since this substance is also converted by the GNE, all of this might yet prove helpful in the development of an appropriate therapy for GNEM.

01 Nov 2023·CNS neuroscience & therapeutics

Increasing brain N-acetylneuraminic acid alleviates hydrocephalus-induced neurological deficits.

Article

Author: Wang, Xin ; Yang, Chen ; Ma, Yuanyuan ; Zhang, Yiying ; Gao, Fang ; Tang, Yanmin ; Nie, Xiaoqun ; Wang, Zhangyang ; Ding, Jing ; Gao, Yanqin

AIMS:

This metabolomic study aimed to evaluate the role of N-acetylneuraminic acid (Neu5Ac) in the neurological deficits of normal pressure hydrocephalus (NPH) and its potential therapeutic effect.

METHODS:

We analyzed the metabolic profiles of NPH using cerebrospinal fluid with multivariate and univariate statistical analyses in a set of 42 NPH patients and 38 controls. We further correlated the levels of differential metabolites with severity-related clinical parameters, including the normal pressure hydrocephalus grading scale (NPHGS). We then established kaolin-induced hydrocephalus in mice and treated them using N-acetylmannosamine (ManNAc), a precursor of Neu5Ac. We examined brain Neu5Ac, astrocyte polarization, demyelination, and neurobehavioral outcomes to explore its therapeutic effect.

RESULTS:

Three metabolites were significantly altered in NPH patients. Only decreased Neu5Ac levels were correlated with NPHGS scores. Decreased brain Neu5Ac levels have been observed in hydrocephalic mice. Increasing brain Neu5Ac by ManNAc suppressed the activation of astrocytes and promoted their transition from A1 to A2 polarization. ManNAc also attenuated the periventricular white matter demyelination and improved neurobehavioral outcomes in hydrocephalic mice.

CONCLUSION:

Increasing brain Neu5Ac improved the neurological outcomes associated with the regulation of astrocyte polarization and the suppression of demyelination in hydrocephalic mice, which may be a potential therapeutic strategy for NPH.

1

News (Medical) associated with N-acetyl-D-mannosamine

27 Apr 2021

·www.biospace.com

LogicBio Therapeutics Announces Research Collaboration with Daiichi Sankyo

LEXINGTON, Mass., April 27, 2021 /PRNewswire/ -- LogicBio Therapeutics, Inc. (LogicBio - Nasdaq: LOGC), a clinical-stage genetic medicine company pioneering gene delivery and gene editing platforms to address rare and serious diseases from infancy through adulthood, today announced the signing of a research collaboration and exclusive option agreement with Daiichi Sankyo Company, Limited (Daiichi Sankyo). Under the terms of the agreement, the companies will collaborate on the development of treatments for two undisclosed indications based on GeneRide™, LogicBio's proprietary gene insertion platform. The agreement also grants Daiichi Sankyo an option to negotiate and acquire worldwide licenses for LogicBio's development programs in these two indications. Financial terms of the collaboration are not disclosed. "I am very pleased to announce this collaboration as a new milestone in the validation of our GeneRide platform. In 2020, we cleared our first Investigational New Drug (IND) application for GeneRide for the treatment of pediatric methylmalonic acidemia (MMA) patients and initiated the Phase 1/2 SUNRISE clinical trial. We also formed our first research agreement with another major pharmaceutical company to develop a drug candidate for Crigler-Najjar syndrome," said Frederic Chereau, president and chief executive officer of LogicBio. "By partnering with Daiichi Sankyo, a global leader in developing innovative medicines, we are reinforcing our commitment to bring innovative therapeutics to people living with serious genetic conditions including many that can present symptoms as early as infancy." The GeneRide platform harnesses a cell's natural DNA repair process leading to durable therapeutic protein expression levels. GeneRide supports the development of a new generation of genetic medicine able to insert a DNA segment into the human genome while potentially avoiding certain risks associated with other gene editing technologies. The therapy uses a viral vector to deliver the therapeutic gene, known as a transgene, to the nuclei of a patient's cells via one-time infusion. LogicBio's two lead development programs based on the GeneRide platform are focused on rare pediatric conditions. The company is currently evaluating LB-001 in the Phase 1/2 SUNRISE trial in MMA and LB-301 in Crigler-Najjar syndrome through another research collaboration. LogicBio is also advancing the development of sAAVyTM, its next-generation AAV capsid platform, designed to overcome limitations with the current generation of AAV-based gene therapies. About LogicBio Therapeutics, Inc. LogicBio Therapeutics is a clinical-stage genetic medicine company pioneering gene delivery and gene editing platforms to address rare and serious diseases from infancy through adulthood. The company's proprietary GeneRide™ platform is a new approach to precise gene insertion that harnesses a cell's natural DNA repair process leading to durable therapeutic protein expression levels. LogicBio's cutting-edge sAAVyTM capsid development platform is designed to support development of treatments in a broad range of indications and tissues. The company is based in Lexington, MA. For more information, visit . Bill Berry Berry & Company Public Relations W: 212-253-8881 C: 917-846-3862 bberry@berrypr.com Jenna Urban Berry & Company Public Relations W: 212-253-8881 C: 203-218-9180 jurban@berrypr.com Company Codes: NASDAQ-NMS:LOGC

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100 Deals associated with N-acetyl-D-mannosamine

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Distal Myopathies	Phase 3	-	National Institutes of Health	-
Distal Myopathies	Phase 3	-	Leadiant Biosciences, Inc.	-
Distal Myopathy, Nonaka Type	Phase 2	US	National Human Genome Research Institute	05 Feb 2015
Kidney Diseases	Phase 1	US	National Institute of Diabetes & Digestive & Kidney Diseases	07 Jul 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02346461 (Pubmed \| Genet Med) Manual	Phase 2	Distal Myopathy, Nonaka Type	12	ManNAc	xwtlpyzoqm(efihqjyjdi) = jgucyuszpe adynffaawa (lqqvzeyafz )	Positive	01 Nov 2021
NCT02639260 (Phase 1 Study of N-Acetylmannosamine (ManNAc) for Glomerular Disease, ASN2020)	Phase 1	Glomerular disease	7	ManNAc 3g single dose	dxfrlfuoms(jjozfuvfun) = There were no serious adverse events. Most subjects (5 of 6) that received ManNAc twice daily showed a marked reduction in urine PCR (26-54%), which correlated with the degree of glomerular hyposialylation wyoqdonaqd (qcdzubhzyu ) View more	Positive	19 Oct 2020
NCT02346461 (CTgov)	Phase 2	Distal Myopathy, Nonaka Type	12	ManNAc (ManNAc: Cohort A)	qfmubaqfuv(yeniwhmhpr) = dbaqgspttx nqglmnfiql (umsyzuvhix, slnzfjjdmh - cslrusgnol) View more	-	16 Apr 2019
NCT02346461 (CTgov)	Phase 2	Distal Myopathy, Nonaka Type	12	ManNAc (ManNAc: Cohort B)	qfmubaqfuv(yeniwhmhpr) = lhnftyejfz nqglmnfiql (umsyzuvhix, fynidepncs - gztmqmsdic) View more	-	16 Apr 2019
ASN2010	Not Applicable	Nephrosis, Lipoid Angptl4 \| NPHS2-Angptl4 \| PAN	-	ManNAc	ehymtrekiy(dknzxlfrjd) = vmqjbamlsn dsgdhkvmdd (fvuffngodf )	Positive	16 Nov 2010