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Methods and compositions related to transplant-associated thrombotic microangiopathy

A technology for microangiopathy and thrombus, applied in the field of evaluation of thrombotic microangiopathy, can solve the problem of lack of screening tools before transplantation

Inactive Publication Date: 2017-08-01
CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is currently no direct approach to address individual susceptibility to transplant-associated TMA, and no pre-transplant screening tools are available to identify subjects at risk for severe TMA

Method used

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  • Methods and compositions related to transplant-associated thrombotic microangiopathy
  • Methods and compositions related to transplant-associated thrombotic microangiopathy
  • Methods and compositions related to transplant-associated thrombotic microangiopathy

Examples

Experimental program
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Effect test

Embodiment 1

[0069] To further explore the mechanism of TMA, we performed a prospective analysis of 17 candidate genes known to play roles in complement activation. See Jodele S, et al., (2015) Blood Nov 24. pii: blood-2015-08-663435. (Electronic publication prior to press), which is hereby incorporated by reference in its entirety.

[0070] research object

[0071] From September 2010 until December 2011, 100 consecutive patients at Cincinnati Children's Hospital Medical Center (CCHMC) who underwent HSCT were enrolled in the prospective TMA biomarker study after institutional review board approval. Using prospective monitoring as previously described, 39% of subjects met the criteria for TMA (Jodele S, et al. (2014) Blood. 124(4):645-653). Diagnostic criteria for TMA include: (1) lactate dehydrogenase (LDH) above the upper limit of normal; (2) platelet count 9 / L or neothrombocytopenia with ≥50% reduction in platelet count; (3) neonatal anemia with hemoglobin below the lower limit of n...

Embodiment 2

[0098] Eighteen patients showing high-risk features of TA-TMA, including nephrotic-range proteinuria and elevated sC5b-9 levels, were treated with eculizumab (Alexion Pharmaceuticals, Cheshire, CT). Dosing levels were adjusted to maintain a therapeutic eculizumab concentration of 100 μg / ml. See Jodele S. et al., (2015), Biol.Blood MarrowTransplant.pii:S1083-8791(15)00672-2.doi:10.1016 / j.bbmt.2015.10.002. (Electronic publication prior to press), refer It is hereby incorporated by reference in its entirety. Total hemolytic complement activity (CH50) and terminal complement activation (sC5b-9) were observed to monitor complement activation and response to therapy. The results of the treated patients were compared with those of the historical controls from our prospective observational study consisting of 11 individuals who had shown the same high-risk features but were not treated with eculizumab. From the onset of TMA diagnosis, overall survival was compared between the two gr...

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Abstract

Embodiments described herein relate to evaluating risk of transplant-associated thrombotic microangiopathy. Disclosed herein are methods for determining the risk of developing transplant-associated thrombotic microangiopathy, as well as the likely severity of the outcome. Some embodiments include selecting and administering a treatment for transplant-associated thrombotic microangiopathy in subjects identified as having elevated risk.

Description

[0001] Incorporation by reference into the priority application [0002] This application claims the benefit of US Provisional Application No. 62 / 094802, filed December 19, 2014, which is hereby incorporated by reference in its entirety. Pursuant to 37 CFR 1.57, any and all applications for which a foreign priority claim or domestic priority claim is identified in the Application Data Sheet filed with this application are hereby incorporated by reference. [0003] field of invention [0004] The present invention relates to systems and methods for assessing the risk of thrombotic microangiopathy, particularly transplant-associated thrombotic microangiopathy. Some embodiments include selecting and administering treatment for transplant-associated thrombotic microangiopathy in subjects identified as having elevated risk. [0005] Background of the invention [0006] Transplant-associated thrombotic microangiopathy (TMA) is a complication associated with hematopoietic stem cell ...

Claims

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Application Information

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IPC IPC(8): A61K39/00
CPCC12Q1/6883C12Q2600/118C12Q2600/158
Inventor 索纳塔·朱迪乐张克健斯特拉·戴维斯
Owner CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
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