Author: Minoru, Tanaka ; Zhao, Guang-Nian ; Zhu, Xueyong ; Zheng, Ankang ; Guo, Sen ; Li, Mingchang ; Zhang, Peng ; Li, Zuo-Zhi ; Xiang, Mei ; Lei, Hao ; Li, Hongliang ; Gong, Jun

Cell-surface receptors provide potential targets for the translation of bench-side findings into therapeutic strategies; however, this approach for the treatment of stroke is disappointing, at least partially due to an incomplete understanding of the targeted factors. Previous studies of oncostatin M (OSM), a member of the gp130 cytokine family, have been limited, as mouse models alone may not strongly resemble the human condition enough. In addition, the precise function of OSM in the CNS remains unclear. Here, we report that human OSM is neuroprotective in vivo and in vitro by recruiting OSMRβ in the setting of ischemic stroke. Using gain- and loss-of-function approaches, we demonstrated that decreased neuronal OSMRβ expression results in deteriorated stroke outcomes but that OSMRβ overexpression in neurons is cerebroprotective. Moreover, administering recombinant human OSM to mice before the onset of I/R showed that human OSM can be protective in rodent models of ischemic stroke. Mechanistically, OSM/OSMRβ activate the JAK2/STAT3 prosurvival signaling pathway. Collectively, these data support that human OSM may represent a promising drug candidate for stroke treatment.SIGNIFICANCE STATEMENTOSM, a member of the gp130 cytokine family, regulates neuronal function and survival. OSM engages a second receptor, either LIFRα or OSMRβ, before recruiting gp130. However, it is not clear whether OSM/OSMRβ signaling is involved in neuroprotection in the setting of ischemic stroke. Recent studies show that, compared with mouse disease models, the OSM receptor system in rats more closely resembles that in humans. In the present study, we use genetic manipulations of OSMRβ in both mouse and rat stroke models to demonstrate that OSMRβ in neurons is critical for neuronal survival during cerebral ischemic/reperfusion. Interestingly, administration of human OSM also leads to improved stroke outcomes. Therefore, OSM may represent a promising drug candidate for stroke treatment.

01 Jan 2014·Mediators of InflammationQ3 · MEDICINE

Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models

Q3 · MEDICINE

ArticleOA

Author: Xing, Dongqi ; Henry, Scott P. ; Graham, Mark J. ; Szalai, Alexander J. ; Crooke, Rosanne M. ; Hage, Fadi G. ; Chen, Yiu-Fai ; Early, Richard ; Oparil, Suzanne ; Zanardi, Thomas A. ; Miller, Andrew ; McCrory, Mark A. ; Mazzone, Michelle

Raised blood C-reactive protein (CRP) level is a predictor of cardiovascular events, but whether blood CRP is causal in the disease process is unknown. The latter would best be defined by pharmacological inhibition of the protein in the context of a randomized case-control study. However, no CRP specific drug is currently available so such a prospective study cannot be performed. Blood CRP is synthesized primarily in the liver and the liver is an organ where antisense oligonucleotide (ASO) drugs accumulate. Taking advantage of this we evaluated the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage. Treating rats for 4 weeks with a rat CRP-specific ASO achieved >60% reduction of blood CRP. Notably, this effect was associated with improved heart function and pathology following myocardial infarction (induced by ligation of the left anterior descending artery). Likewise in human CRP transgenic mice treated for 2 weeks with a human CRP-specific ASO, blood human CRP was reduced by >70% and carotid artery patency was improved (2 weeks after surgical ligation). CRP specific ASOs might pave the way towards a placebo-controlled trial that could clarify the role of CRP in cardiovascular disease.

01 Jan 2013·Journal of Diabetes and its ComplicationsQ3 · MEDICINE

Human C-reactive protein accentuates macrophage activity in biobreeding diabetic rats

Q3 · MEDICINE

Article

Author: Harmeet Kaur ; Ishwarlal Jialal ; Sridevi Devaraj

OBJECTIVEType 1 diabetes (T1DM) is a pro-inflammatory state characterized by high C-reactive protein (CRP) levels. However, there is a paucity of data examining the role of CRP in promoting the pro-inflammatory state of diabetes. Thus, we examined the pro-inflammatory effects of human CRP using spontaneously diabetic bio-breeding (BB) rats.METHODSDiabetic rats (n=9/group) were injected with Human serum albumin (huSA) or Human CRP (hCRP, 20 mg/kg body weight; i.p.) for 3 consecutive days. Blood and peritoneal macrophages (MØ) were obtained following euthanasia. Peritoneal macrophages were used for measuring superoxide anion release, NF-κB DNA binding activity, proinflammatory mediator secretion.RESULTShCRP administration resulted in significantly increased superoxide anion production, along with increased release of cytokines/chemokines, and plasminogen activator inhibitor (PAI-1) and Tissue Factor (TF) activity in diabetic rats compared to huSA. hCRP-treated BB rat MØ showed significant induction of protein kinase C (PKC)-alpha, PKC-delta and p47 phox expression and NF-κB compared to huSA.CONCLUSIONSThus, our data suggest that human CRP exacerbates in-vivo the pro-inflammatory, pro-oxidant and procoagulant states of diabetes predominantly via increased macrophage activity and this could have implications with respect to vascular complications and anti-inflammatory therapies.

100 Deals associated with Human Rhodopsin(Kubota Vision)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Retinitis Pigmentosa	Preclinical	US	The University of Manchester	30 Mar 2016

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Human Rhodopsin(Kubota Vision)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation