Preventative and therapeutic effects of a novel humanized anti-glycoprotein Ibα fragment of antigen-binding region in a murine model of thrombotic thrombocytopenic purpura

Article

Author: Ma, Wenjing ; Liu, Zhenze ; Zheng, Liang ; Adili, Reheman ; Ni, Heyu ; Zheng, X Long ; Xu, Xiaohong Ruby ; Slavkovic, Sladjana ; Wu, Zhijian ; Zhang, Quan ; Zhu, Guangheng ; Neves, Miguel A D ; Lei, Xi

BACKGROUNDThrombotic thrombocytopenic purpura (TTP) is a potentially fatal blood disorder, resulting from severe deficiency of plasma ADAMTS13 activity. Current treatment for immune-mediated TTP includes daily therapeutic plasma exchange (TPE), plus caplacizumab and immunosuppressives. For hereditary TTP, resulting from mutations of ADAMTS13, plasma infusion or recombinant ADAMTS13 is the treatment of choice. However, there are still unmet needs for an effective alternative therapy for TTP.OBJECTIVEThe present study aims to evaluate therapeutic efficacy of a novel humanized antibody Fab fragment against platelet glycoprotein Ibα (CA1001) in a murine model of TTP.METHODSPlatelet agglutination profiles, microfluidic shear-based assay, and intravital microscopy thrombosis model, as well as lysine histone-induced murine "TTP-like" model were employed.RESULTSCA1001 exhibits potent inhibition of botrocetin-induced murine platelet agglutination in a dose and time-dependent manner. CA1001 also significantly inhibits shear-dependent adhesion and aggregation of murine platelets to endothelial von Willebrand factor (VWF) released from calcium ionophore activated cremaster venules in Adamts13^-/- mice and blocks the formation of platelet-VWF rich thrombosis. More importantly, CA1001 appears to be efficacious in preventing and treating a histone-induced "TTP-like" syndrome in Adamts13^-/- mice, demonstrated by the allievation of thrombocytopenia, prerenal injury, and the formation of microvascular thrombosis in major organ tissues.CONCLUSIONSCA1001 can effectively inhibit VWF-platelet interaction and thrombus formation under various (patho)physiological conditions. Thus, CA1001 may be a potential candidate for further development as a novel therapeutic for immune-mediated and hereditary TTP and perhaps for other inflammatory thrombotic disorders such as ischemic stroke.

01 Dec 2018·Journal of Genetic Engineering and Biotechnology

Optimization of indole acetic acid production by isolated bacteria from Stevia rebaudiana rhizosphere and its effects on plant growth

Article

Author: Askari, Kazim ; Kumari, Madhumita ; Chandra, Sheela

The ability to synthesize Indole-3-acetic acid (IAA) is widely associated with the plant growth promoting rhizobacteria (PGPR). The present work deals with isolation and characterization of such bacteria from the rhizosphere of medicinal plant Stevia rebaudiana and optimization of IAA production from its isolates. The optimization of IAA production was carried out at different pH and temperature with varied carbon and nitrogen sources of culture media. Out of different isolates obtained, three of them were screened as efficient PGPRs on the basis of different plant growth promoting attributes. Isolates CA1001 and CA2004 showed better production of IAA at pH 9 (91.7 µg ml^-1) and at temperature 37 °C (81.7 µg ml^-1). Dextrose (1%) was found to be the best carbon source for isolate CA1001 with 104 µg ml^-1 IAA production. Isolate CA 2004 showed best production of IAA 36 µg ml^-1 and 34 µg ml^-1 at 1.5% and 1% Beef extract as nitrogen source respectively. Isolate CA 1001 showed 32 µg ml^-1 IAA production at 0.5% nicotinic acid concentration. From the current study, CA1001 and CA2004 emerged as noble alternatives for IAA production further which also resulted in root and shoot biomass generation in crop plants, hence can be further used as bio-inoculants for plant growth promotion.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	IND Approval	China	Sisioai (Hangzhou) Biomedical Co., Ltd.	12 Nov 2024
Hyperalgesia	Preclinical	United States	Oakland University	-

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