Phase III Clinical Trial of Y-3 for Injection in the Treatment of Acute Ischemic Stroke - A Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Phase III Clinical Study

Start Date24 Jul 2024

Sponsor / Collaborator-

NCT06517173 / RecruitingPhase 3IIT

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Y-3 in Chinese Subjects with Acute Ischemic Stroke

This trial aims to evaluate the effectiveness and safety of Y-3 for injection in the treatment of patients with acute ischemic stroke within 48 hours of onset

Start Date24 Jul 2024

Sponsor / Collaborator

Beijing Tiantan Hospital

[+1]

CTR20242311 / RecruitingPhase 3

注射用Y-3治疗急性缺血性卒中III期临床试验——多中心、随机、双盲、平行、安慰剂对照III期临床研究

[Translation] Phase III clinical trial of Y-3 injection in the treatment of acute ischemic stroke - a multicenter, randomized, double-blind, parallel, placebo-controlled phase III clinical study

评价注射用Y-3治疗发病在48h以内的急性缺血性卒中患者的有效性和安全性

[Translation]

To evaluate the efficacy and safety of Y-3 for injection in the treatment of patients with acute ischemic stroke within 48 hours of onset

Start Date24 Jul 2024

Sponsor / Collaborator

Nanjing Ningdan New Drug Technology Co., Ltd.

100 Clinical Results associated with PSD95 x nNOS

100 Translational Medicine associated with PSD95 x nNOS

0 Patents (Medical) associated with PSD95 x nNOS

181

Literatures (Medical) associated with PSD95 x nNOS

01 Oct 2024·Biochemical and Biophysical Research Communications

Combinatorial therapy with sub-effective Ro25-6981 and ZL006 ameliorates depressive-like behavior in single or combined stressed male mice

Article

Author: Fang, Weiqing ; Wang, Xuemeng ; Liu, Yixiu ; Lu, Wen ; Yao, Yilan

Major depression is a severe neuropsychiatric disorder that poses a significant challenge to health. However, development of an effective therapy for the disease has long been difficult. Here, we investigate the efficacy of a novel combinatorial treatment employing sub-effective doses of Ro25-6981, an antagonist targeting GluN2B-containing NMDA receptors, in conjunction with ZL006, an inhibitor of the PSD95/nNOS, on mouse models of depression. We employed social isolation, chronic restraint stress, or a combination of both to establish a depressed mouse model. Treatment with the drug combination reduced depressive-like behaviors without affecting locomotor activity in mice subjected to social isolation or chronic restraint stress. Furthermore, the combination therapy ameliorated depressive-like behaviors induced by combined stress of chronic restraint followed by social isolation. Mechanistic studies revealed that the combined treatment downregulated the hippocampal nitric oxide level. However, the therapeutic benefits of this combination were negated by the activation of NMDA receptors with a low dose of NMDA or by increasing nitric oxide levels with l-arginine. Moreover, the combinatorial treatment had negligible effects on object memory and contextual fear memory. Our data establish a combined therapy paradigm, providing a potential strategy targeting major depression.

16 Sep 2024·Molecular neurobiology

PSD-95 Protein: A Promising Therapeutic Target in Chronic Pain.

Review

Author: Li, Jing ; Yuan, Jie ; Cao, Song ; Ma, Lulin ; Tan, Xinran ; Wen, Song ; Sun, Dongdong

Chronic pain, as a social public health problem, has a serious impact on the quality of patients' life. Currently, the main drugs used to treat chronic pain are opioids, antipyretic, and nonsteroidal anti-inflammatory drugs (NSAIDs). But the obvious side effects limit their use, so it is urgent to find new therapeutic targets. Postsynaptic density (PSD)-95 protein plays an important role in the occurrence and development of chronic pain. The over-expression of the PSD-95 protein and its interaction with other proteins are closely related to the chronic pain. Besides, the PSD-95-related drugs that inhibit the expression of PSD-95 as well as the interaction with other protein have been proved to treat chronic pain significantly. In conclusion, although more deep studies are needed in the future, these studies indicate that PSD-95 and the related proteins, such as NMDA receptor (NMDAR) subunit 2B (GluN2B), AMPA receptor (AMPAR), calmodulin-dependent protein kinase II (CaMKII), 5-hydroxytryptamine 2A receptor (5-HT2AR), and neuronal nitric oxide synthase (nNOS), are the promising therapeutic targets for chronic pain.

01 Jul 2024·Heliyon

NMDA receptor remodeling and nNOS activation in mice after unilateral striatal injury with 6-OHDA

Article

Author: Silva, Andrea Alice ; da Cunha Faria-Melibeu, Adriana ; Cossenza, Marcelo ; de Carvalho, Michele Barboza ; Serfaty, Claudio Alberto ; Campello-Costa, Paula ; Marques, Suelen Adriani ; Teixeira-Silva, Bruna

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by selective dopaminergic loss. Non dopaminergic neurotransmitters such as glutamate are also involved in PD progression. NMDA receptor/postsynaptic density protein 95 (PSD-95)/neuronal nitric oxide synthase (nNOS) activation is involved in neuronal excitability in PD. Here, we are focusing on the evaluating these post-synaptic protein levels in the 6-OHDA model of PD. Adult male C57BL/6 mice subjected to unilateral striatal injury with 6-OHDA were assessed at 1-, 2-, or 4-weeks post-lesion. Animals were subjected to an apomorphine-induced rotation test followed by the analysis of protein content, synaptic structure, and NOx production. All biochemical analysis was performed comparing the control versus lesioned sides of the same animal. 6-OHDA mice exhibited contralateral rotation activity, difficulties in coordinating movements, and changes in Iba-1 and glial fibrillary acidic protein (GFAP) expression during the whole period. At one week of survival, the mice showed a shift in NMDA composition, favoring the GluN2A subunit and increased PSD95 and nNOS expression and NOx formation. After two-weeks, a decrease in the total number of synapses was observed in the lesioned side. However, the number of excitatory synapses was increased with a higher content of GluN1 subunit and PSD95. After four weeks, NMDA receptor subunits restored to control levels. Interestingly, NOx formation in the serum increased. This study reveals, for the first time, the temporal course of behavioral deficits and glutamatergic synaptic plasticity through NMDAr subunit shift. Together, these data demonstrate that dopamine depletion leads to a fine adaptive response over time, which can be used for further studies of therapeutic management adjustments with the progression of PD.

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