NIB101-01 study is an open-label, non-randomized Phase 1 study in participants with GM2 positive advanced solid tumor, who failed to available standard of cares to evaluate the safety and tolerability of NIB101.

开始日期2022-01-24

申办/合作机构

Noile-Immune Biotech, Inc.

JPRN-jRCT2033210499 / Recruiting临床1期IIT

An Open-Label Non-Randomized Phase 1 Dose Escalation and Dose Expansion Study of NIB101 in Participants with Advanced Solid Tumors

开始日期2021-12-27

申办/合作机构-

NCT01898156 / Terminated临床1/2期

Two-Part, Open-Label, Multi-Center, Phase 1/2 Study of Anti-GM2 Ganglioside Monoclonal Antibody BIW-8962 as Monotherapy in Subjects With Previously Treated Advanced/Recurrent Lung Cancer or Mesothelioma

This Phase 1/2 study is designed to assess the following: safety and tolerability of BIW-8962, Dose Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D) in Phase 1 in subjects with advanced/recurrent lung cancers or mesothelioma and preliminary efficacy in Phase 2 in subjects with advanced/recurrent Small Cell Lung Cancer.

开始日期2013-07-01

申办/合作机构

Kyowa Kirin Korea Co., Ltd.

100 项与 GM2(ganglioside M2) 相关的临床结果

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100 项与 GM2(ganglioside M2) 相关的转化医学

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0 项与 GM2(ganglioside M2) 相关的专利（医药）

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项与 GM2(ganglioside M2) 相关的文献（医药）

2024-08-01·Transplant Immunology

Intraperitoneal injection of mesenchymal stem cells-conditioned media (MSCS-CM) treated monocyte can potentially alleviate motor defects in experimental autoimmune encephalomyelitis female mice; An original experimental study

Article

作者: Ghorbani Alvanegh, Akbar ; Raei, Mahdi ; Jalali Kondori, Bahman ; Esmaeili Gouvarchin Ghaleh, Hadi ; Abdolmaleki, Amir

INTRODUCTIONMultiple sclerosis (MS), as a destructive pathology of myelin in central nervous system (CNS), causes physical and mental complications. Experimental autoimmune encephalomyelitis (EAE) is laboratory model of MS widely used for CNS-associated inflammatory researches. Cell therapy using macrophage M2 (MPM2) is a cell type with anti-inflammatory characteristics for all inflammatory-based neuropathies. This experimental study investigated the probable therapeutic anti-inflammatory effects of intraperitoneal (IP) injection of MPM2 on alleviation of motor defect in EAE-affected animals.MATERIALS AND METHODS24 C57/BL6 female mice were divided into four groups of EAE, EAE + Dexa, EAE + PBS, and EAE + MP2. EAE was induced through deep cervical injection of spinal homogenate of guinea pigs. MPM2 cells were harvested from bone marrow and injected (10⁶cells/ml) in three days of 10, 13 and 16 post-immunizations (p.i). Clinical score (CS), anti-inflammatory cytokines (IL-4, IL-10), pro-inflammatory gene expression (TNF-α, IL-1β) and histopathological investigations (HE, Nissl and Luxol Fast Blue) were considered. Data were analyzed using SPSS software (v.19) and p < 0.05 was considered significant level.RESULTSDuring EAE induction, the mean animal weight was decreased (p < 0.05); besides, following MPM2 injection, the weight gain was applied (p < 0.05) in EAE + MPM2 groups than control. Increased (p < 0.05) levels of CS was found during EAE induction in days 17-28 in EAE animals; besides, CS was decreased (p < 0.05) in EAE + MPM2 group than EAE animals. Also, in days 25-28 of experiment, the CS was decreased (p < 0.05) in EAE + MPM2 than EAE + Dexa. Histopathological assessments revealed low density of cell nuclei in corpus callosum, microscopically. LFB staining also showed considerable decrease in white matter density of corpus callosum in EAE group. Acceleration of white matter density was found in EAE + MPM2 group following cell therapy procedure. Genes expression of TNF-α, IL-1β along with IL-4 and IL-10 were decreased (p < 0.05) in EAE + MPM2 group.CONCLUSIONIP injection of MPM2 to EAE-affected female mice can potentially reduce the CNS inflammation, neuronal death and myelin destruction. MPM2 cell therapy can improve animal motor defects.

2024-08-01·Biophysical Journal

Conformations of influenza A M2 protein in DOPC/DOPS and E. coli native lipids and proteins

Article

作者: Sanders, Griffin ; Georgieva, Elka R ; Borbat, Peter P

We compared the conformations of the transmembrane domain (TMD) of influenza A M2 (IM2) protein reconstituted in 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPC/DOPS) bilayers to those in isolated Escherichia coli (E. coli) membranes, having preserved its native proteins and lipids. IM2 is a single-pass transmembrane protein known to assemble into a homo-tetrameric proton channel. To represent this channel, we made a construct containing the IM2's TMD region flanked by the juxtamembrane residues. The single cysteine substitution, L43C, of leucine located in the bilayer polar region was paramagnetically tagged with a methanethiosulfonate nitroxide label for the electron spin resonance (ESR) study. For this particular residue, we probed the conformations of the spin-labeled IM2 reconstituted in DOPC/DOPS and isolated E. coli membranes using continuous-wave ESR and double electron-electron resonance (DEER) spectroscopy. The total protein-to-lipid molar ratio spanned the range from 1:230 to 1:10,400. The continuous-wave ESR spectra corresponded to very slow spin-label motion in both environments. In all cases, the DEER data were reconstructed into distance distributions with well-resolved peaks at 1.68 and 2.37 nm in distance and amplitude ratios of 1.41 ± 0.2 and 2:1, respectively. This suggests four nitroxide spin labels located at the corners of a square, indicative of an axially symmetric tetramer. The distance modeling of DEER data with molecular modeling software applied to the NMR molecular structures (PDB: 2L0J) confirmed the symmetry and closed state of the C-terminal exit pore of the IM2 TMD tetramer in agreement with the model. Thus, we can conclude that, under conditions of pH 7.4 used in this study, IM2 TMD has similar conformations in model lipid bilayers and membranes made of native E. coli lipids and proteins of comparable thickness and fluidity, notwithstanding the complexity of the E. coli membranes caused by their lipid diversity and the abundance of integral and peripheral membrane proteins.

2024-05-01·Journal of Child Neurology

Development of an Infantile GM2 Clinical Rating Scale: Remote Assessment of Clinically Meaningful Health-Related Function

Article

作者: Eichler, Florian S ; Kiefer, Michael ; Simione, Meg ; Townsend, Elise L

GM2 gangliosidoses (GM2) are a group of rare lysosomal storage disorders in which accumulation of GM2 gangliosides results in progressive central nervous system damage. The infantile GM2 phenotype is characterized by delays in milestones by 6 months of age, followed by rapid loss of motor, cognitive, and visual function. Advancements in early diagnosis and pharmacotherapies provide promise for improved outcomes. However, the lack of feasible and clinically meaningful clinical outcome assessments for GM2 poses a challenge to characterizing GM2 natural history and selecting clinical trial endpoints. The purpose of this study was to develop a remotely administered infantile GM2 rating scale to measure health-related function in children with infantile GM2. A 2-phase mixed methods design was employed. In phase 1 of the study, 8 families of children with Infantile GM2 completed a natural history survey and a 1:1 semistructured interview to provide caregiver perspectives on the impacts of GM2 on health-related function. In phase 2 of the study, 8 expert clinicians provided feedback via surveys and participated in videoconference-hosted focus groups to refine scale administration and scoring procedures. These methods guided the development of 16 scale items to assess function in 5 health-related function domains: vision, hand and arm use, communication, gross motor, and feeding. This study used caregiver perspectives and expert clinician feedback to develop a remotely administered clinical outcome assessment of clinically meaningful health-related function in children with infantile GM2. Future studies will further evaluate the feasibility, reliability, and validity of the Infantile GM2 Clinical Rating Scale.

项与 GM2(ganglioside M2) 相关的新闻（医药）

2022-11-04

·生物谷

Mol Neurodegener：科学家识别出一种或会诱发人类阿尔兹海默病发生的特殊蛋白质

来自美国布莱根妇女医院等机构的科学家们通过研究识别出了一种会促进机体患阿尔兹海默病的新型蛋白。阿尔兹海默病目前尚无有效的治愈性手段，预计到2050年阿尔兹海默病将会在全球影响超过1亿人的健康，目前正在进行的研究重点关注两种关键的神经毒性蛋白，即β淀粉样蛋白（Aβ）和tau蛋白，由于这两种蛋白被认为与阿尔兹海默病发病直接相关，对于某些患病人群而言，Aβ和tau蛋白的水平或许并不能持续解释或与患者大脑认知功能下降的严重程度有关。近日，一篇发表在国际杂志Molecular Neurodegeneration上题为“Elevated ganglioside GM2 activator (GM2A) in human brain tissue reduces neurite integrity and spontaneous neuronal activity”的研究报告中，来自美国布莱根妇女医院等机构的科学家们通过研究识别出了一种会促进机体患阿尔兹海默病的新型蛋白。科学家识别出一种或会诱发人类阿尔兹海默病发生的特殊蛋白质。图片来源：Molecular Neurodegeneration (2022). DOI: 10.1186/s13024-022-00558-4 文章中，研究人员为了识别出直接参与阿尔兹海默病基本方面的其它蛋白质，比如突触的缺失或神经退行性病变，他们将实验室中的神经元暴露于来自大约40名个体的大脑提取物中，这些个体要么患有阿尔兹海默病，要么尽管大脑中含有高水平的Aβ和tau蛋白，其仍然被保护免于患阿尔兹海默病，或者尽管其免于患阿尔兹海默病，但大脑中有很少或没有Aβ和tau蛋白。研究人员识别并证实了神经节苷脂GM2激活子（GM2A，ganglioside GM2 activator）或能作为一种特殊蛋白来减少神经元的“发射”并诱导神经元完整性的丧失，这些蛋白质的特性有助于诱发阿尔兹海默病以及疾病的进展。研究者Tracy Young-Pearse说道，本文研究数据或能帮助识别出一种新型和潜在重要的蛋白质，其或与阿尔兹海默病的病理学表现存在一定关联；有意思的是，GM2A此前被认为作为一种致病性因子参与到了溶酶体储积症的发病过程中，而溶酶体储积症与戴萨克斯症(Tay-Sachs disease)非常相似，戴萨克斯症又是一种另一种像阿尔兹海默病一样破坏神经元的疾病。综上，本文研究中，研究人员引入了一种特殊系统用于模拟神经元的易感性，从而对人类大脑中存在的特殊因子产生反应，同时还提供了关于潜在诱发人类阿尔兹海默病发生的蛋白质的相关见解。（生物谷Bioon.com）原始出处： Yi-Chen Hsieh, Joseph Negri, Amy He, et al. Elevated ganglioside GM2 activator (GM2A) in human brain tissue reduces neurite integrity and spontaneous neuronal activity, Molecular Neurodegeneration (2022). DOI: 10.1186/s13024-022-00558-4