更新于：2024-11-01

IgG x APP

更新于：2024-11-01

基本信息

关联

项与 IgG x APP 相关的药物

AT-02 (Attralus)

靶点

APP x IgG

作用机制

APP抑制剂 [+1]

在研机构

Attralus, Inc.初创企业 [+1]

原研机构

University of Tennessee [+1]

在研适应症

免疫球蛋白轻链淀粉样变性 [+2]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 IgG x APP 相关的临床试验

NCT05951049 / Recruiting临床2期

A Phase 2, Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of AT-02

This is a Phase 2 open-label extension study to evaluate the long-term safety, tolerability, and clinical activity of AT-02.
AT-02 is an investigational medicinal product being developed to treat systemic amyloidosis.

开始日期2023-09-21

申办/合作机构

Attralus, Inc.初创企业

[+1]

NCT05521022 / Recruiting临床1期

A Three-part, Phase 1, Single-ascending, and Multiple-ascending Dose Escalation Study in Healthy Volunteers and Subjects With Systemic Amyloidosis to Assess the Safety, Tolerability, and Pharmacokinetics of AT-02

This is a multicenter, international, three-part, Phase 1 study designed to evaluate the safety, tolerability, and PK of rising single doses of AT-02 in healthy volunteers and in subjects with systemic amyloidosis and to assess the safety, tolerability, and PK of multiple doses of AT-02 in subjects with systemic amyloidosis.

开始日期2022-09-01

申办/合作机构

Attralus, Inc.初创企业

[+1]

100 项与 IgG x APP 相关的临床结果

登录后查看更多信息

100 项与 IgG x APP 相关的转化医学

登录后查看更多信息

0 项与 IgG x APP 相关的专利（医药）

登录后查看更多信息

项与 IgG x APP 相关的文献（医药）

2021-02-12·Brain1区 · 医学

Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury

1区 · 医学

Article

作者: Schwab, Jan M ; Berger, Thomas ; Schwaiger, Carmen ; Zrzavy, Tobias ; Wimmer, Isabella ; Lassmann, Hans ; Butovsky, Oleg ; Höftberger, Romana ; Bauer, Jan

AbstractTraumatic spinal cord injury is a devastating insult followed by progressive cord atrophy and neurodegeneration. Dysregulated or non-resolving inflammatory processes can disturb neuronal homeostasis and drive neurodegeneration. Here, we provide an in-depth characterization of innate and adaptive inflammatory responses as well as oxidative tissue injury in human traumatic spinal cord injury lesions compared to non-traumatic control cords. In the lesion core, microglia were rapidly lost while intermediate (co-expressing pro- as well as anti-inflammatory molecules) blood-borne macrophages dominated. In contrast, in the surrounding rim, TMEM119+ microglia numbers were maintained through local proliferation and demonstrated a predominantly pro-inflammatory phenotype. Lymphocyte numbers were low and mainly consisted of CD8+ T cells. Only in a subpopulation of patients, CD138+/IgG+ plasma cells were detected, which could serve as candidate cellular sources for a developing humoral immunity. Oxidative neuronal cell body and axonal injury was visualized by intracellular accumulation of amyloid precursor protein (APP) and oxidized phospholipids (e06) and occurred early within the lesion core and declined over time. In contrast, within the surrounding rim, pronounced APP+/e06+ axon-dendritic injury of neurons was detected, which remained significantly elevated up to months/years, thus providing mechanistic evidence for ongoing neuronal damage long after initial trauma. Dynamic and sustained neurotoxicity after human spinal cord injury might be a substantial contributor to (i) an impaired response to rehabilitation; (ii) overall failure of recovery; or (iii) late loss of recovered function (neuro-worsening/degeneration).

2018-10-01·Journal of Neurotrauma2区 · 医学

Contribution of Fibrinogen to Inflammation and Neuronal Density in Human Traumatic Brain Injury

2区 · 医学

Article

作者: Craner, Matthew J. ; Esiri, Margaret M. ; Jenkins, Damian R. ; DeLuca, Gabriele C.

Traumatic brain injury (TBI) is a leading cause of death and disability, particularly among the young. Despite this, no disease-specific treatments exist. Recently, blood-brain barrier disruption and parenchymal fibrinogen deposition have been reported in acute traumatic brain injury and in long-term survival; however, their contribution to the neuropathology of TBI remains unknown. The presence of fibrinogen-a well-documented activator of microglia/macrophages-may be associated with neuroinflammation, and neuronal/axonal injury. To test this hypothesis, cases of human TBI with survival times ranging from 12 h to 13 years (survival <2 months, n = 15; survival >1 year, n = 6) were compared with uninjured controls (n = 15). Tissue was selected from the frontal lobe, temporal lobe, corpus callosum, cingulate gyrus, and brainstem, and the extent of plasma protein (fibrinogen and immunoglobulin G [IgG]) deposition, microglial/macrophage activation (CD68 and ionized calcium-binding adapter molecule 1 [Iba-1] immunoreactivity), neuronal density, and axonal transport impairment (β-amyloid precursor protein [βAPP] immunoreactivity) were assessed. Quantitative analysis revealed a significant increase in parenchymal fibrinogen and IgG deposition following acute TBI compared with long-term survival and control. Fibrinogen, but not IgG, was associated with microglial/macrophage activation and a significant reduction in neuronal density. Perivascular fibrinogen deposition also was associated with microglial/macrophage clustering and accrual of βAPP in axonal spheroids, albeit rarely. These findings mandate the future exploration of causal relationships between fibrinogen deposition, microglia/macrophage activation, and potential neuronal loss in acute TBI.

2018-01-01·Korean Journal of Radiology3区 · 医学

Blood-Brain Barrier Disruption and Perivascular Beta-Amyloid Accumulation in the Brain of Aged Rats with Spontaneous Hypertension: Evaluation with Dynamic Contrast-Enhanced Magnetic Resonance Imaging

3区 · 医学

Article

作者: Gao, Fabao ; Zheng, Jie ; Chen, Wei ; Wang, Chunhua ; Zhang, Ruzhi ; Wang, Yu ; Xu, Ziqian ; Song, Li ; Tao, Chuanyuan

ObjectiveWhether blood-brain barrier (BBB) disruption induced by chronic spontaneous hypertension is associated with beta-amyloid (Aβ) accumulation in the brain remains poorly understood. The purpose of this study was to investigate the relationship between BBB disruption and Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension.Materials and MethodsFive aged spontaneously hypertensive rats (SHRs) and five age-matched normotensive Wistar-Kyoto (WKY) rats were studied. The volume transfer constant (K^trans) obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to evaluate BBB permeability in the hippocampus and cortex in vivo. The BBB tight junctions, immunoglobulin G (IgG), Aβ, and amyloid precursor protein (APP) in the hippocampus and cortex were examined with immunohistochemistry.ResultsAs compared with WKY rats, the K^trans values in the hippocampus and cortex of the SHRs increased remarkably (0.316 ± 0.027 min^-1 vs. 0.084 ± 0.017 min^-1, p < 0.001 for hippocampus; 0.302 ± 0.072 min^-1 vs. 0.052 ± 0.047 min^-1, p < 0.001 for cortex). Dramatic occludin and zonula occludens-1 losses were detected in the hippocampus and cortex of SHRs, and obvious IgG exudation was found there. Dramatic Aβ accumulation was found and limited to the area surrounding the BBB, without extension to other parenchyma regions in the hippocampus and cortex of aged SHRs. Alternatively, differences in APP expression in the hippocampus and cortex were not significant.ConclusionBlood-brain barrier disruption is associated with Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. DCE-MRI can be used as an effective method to investigated BBB damage.