更新于：2024-11-01

Anemia, Hypochromic Microcytic, With Iron Overload

小细胞低色素性贫血伴铁过载

更新于：2024-11-01

基本信息

别名

ANEMIA, HYPOCHROMIC MICROCYTIC, WITH IRON OVERLOAD、Anemia, Hypochromic Microcytic, With Iron Overload、Hypochromic microcytic anaemia with iron overload

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简介

A congenital hypochromic microcytic anemia with progressive liver iron overload paradoxically associated with normal to moderately elevated serum ferritin levels has been described in three unrelated patients.

关联

项与小细胞低色素性贫血伴铁过载相关的药物

XEN602

靶点

Nramp2

作用机制

Nramp2抑制剂

在研机构

Xenon Pharmaceuticals, Inc.

原研机构

Xenon Pharmaceuticals, Inc.

在研适应症

小细胞低色素性贫血伴铁过载

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与小细胞低色素性贫血伴铁过载相关的临床试验

NCT04631718 / CompletedN/AIIT

MRI-based Quantitative Susceptibility Mapping of Hepatic Iron Overload

The overall goal of this project is to develop and validate a novel technique for Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM) of the abdomen, for non-invasive assessment of liver iron deposition. In this work, study team will develop and optimize advanced data acquisition and image reconstruction methods to enable QSM of the abdomen. Further, investigators will determine the accuracy, repeatability, and reproducibility of abdominal QSM for iron quantification in patients with liver iron overload.
Excessive accumulation of iron in various organs, including the liver, which affects both adult and pediatric populations, is toxic and requires treatment aimed at reducing body iron stores. Accurate assessment of liver iron concentration is critical for the detection and staging of iron overload as well as for longitudinal monitoring during treatment.
In summary, this project will develop a novel MRI-based QSM technique designed for the abdomen and will validate it in pediatric and adult patients with liver iron overload. Upon successful validation, QSM will provide accurate, repeatable, and reproducible quantification of LIC based on a fundamental property of tissue.

开始日期2022-01-18

申办/合作机构

University of Wisconsin Madison

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100 项与小细胞低色素性贫血伴铁过载相关的临床结果

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100 项与小细胞低色素性贫血伴铁过载相关的转化医学

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0 项与小细胞低色素性贫血伴铁过载相关的专利（医药）

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项与小细胞低色素性贫血伴铁过载相关的文献（医药）

2021-07-01·British Journal of Haematology2区 · 医学

SLN124, a GalNac‐siRNA targeting transmembrane serine protease 6, in combination with deferiprone therapy reduces ineffective erythropoiesis and hepatic iron‐overload in a mouse model of β‐thalassaemia

2区 · 医学

Article

作者: Eisermann, Mona ; Vadolas, Jim ; Grigoriadis, George ; Nualkaew, Tiwaporn ; Schaeper, Ute ; Kysenius, Kai ; Crouch, Peter J. ; Dames, Sibylle ; Vilcassim, Shahla ; Ng, Garrett Z.

SummaryBeta‐thalassaemia is an inherited blood disorder characterised by ineffective erythropoiesis and anaemia. Consequently, hepcidin expression is reduced resulting in increased iron absorption and primary iron overload. Hepcidin is under the negative control of transmembrane serine protease 6 (TMPRSS6) via cleavage of haemojuvelin (HJV), a co‐receptor for the bone morphogenetic protein (BMP)‐mothers against decapentaplegic homologue (SMAD) signalling pathway. Considering the central role of the TMPRSS6/HJV/hepcidin axis in iron homeostasis, the inhibition of TMPRSS6 expression represents a promising therapeutic strategy to increase hepcidin production and ameliorate anaemia and iron overload in β‐thalassaemia. In the present study, we investigated a small interfering RNA (siRNA) conjugate optimised for hepatic targeting of Tmprss6 (SLN124) in β‐thalassaemia mice (Hbbth3/+). Two subcutaneous injections of SLN124 (3 mg/kg) were sufficient to normalise hepcidin expression and reduce anaemia. We also observed a significant improvement in erythroid maturation, which was associated with a significant reduction in splenomegaly. Treatment with the iron chelator, deferiprone (DFP), did not impact any of the erythroid parameters. However, the combination of SLN124 with DFP was more effective in reducing hepatic iron overload than either treatment alone. Collectively, we show that the combination therapy can ameliorate several disease symptoms associated with chronic anaemia and iron overload, and therefore represents a promising pharmacological modality for the treatment of β‐thalassaemia and related disorders.

2016-02-01·Liver International2区 · 医学

Resveratrol mediates therapeutic hepatic effects in acquired and genetic murine models of iron‐overload

2区 · 医学

Article

作者: DesAulniers, Jessica ; Dyck, Jason R. B. ; Kassiri, Zamaneh ; Das, Subhash K. ; Oudit, Gavin Y.

AbstractBackground & AimsAbnormal iron metabolism and hepatic iron‐overload is a major cause of liver injury and in the development of chronic liver diseases. Iron‐overload‐mediated liver disease leads to end‐stage cirrhosis and/or hepatocellular carcinoma.MethodsUsing a genetic hemochromatosis (hemojuvelin knockout mice) and non‐genetic (secondary iron‐overload) murine models of hepatic iron‐overload, we elucidated the mechanism of hepatic iron injury and the therapeutic effects of resveratrol.ResultsHepatic iron‐overload was associated with hepatosplenomegaly, increased oxidative stress, hepatic fibrosis, and inflammation, and a pro‐apoptotic state which was markedly corrected by resveratrol therapy. Importantly our aging studies with the hemojuvelin knockout mice showed advanced liver disease in association with steatosis in the absence of a diabetic state which recapitulates the essential pathological features seen in clinical iron‐overload. Chronic hepatic iron‐overload showed increased nuclear localization of acetylated Forkhead fox‐O‐1 (FoxO1) transcription factor whereas resveratrol dietary intervention reversed the acetylation of FoxO1 in association with increased SIRT1 levels which together with its pleotropic antioxidant properties are likely key mechanisms of its therapeutic action. Importantly, resveratrol treatment did not affect the degree of hepatic iron‐overload but rather direct protects the liver from iron‐mediated injury.ConclusionsOur findings illustrate a novel and definitive therapeutic action of resveratrol and represent an economically feasible therapeutic intervention to treat hepatic iron‐overload and liver disease.

2013-12-01·European Journal of Radiology2区 · 医学

Diagnostic value of real-time elastography in the assessment of hepatic fibrosis in patients with liver iron overload

2区 · 医学

Article

作者: Marta Pongiglione ; Francesco Paparo ; Luca Cevasco ; Manuela Balocco ; Daniele Zefiro ; Gian Luca Forni ; Lorenzo Bacigalupo ; Ennio Biscaldi ; Gian Andrea Rollandi ; Simone Banderali

OBJECTIVEThe objective of our prospective monocentric work was to determine the diagnostic value of real-time elastography (RTE) in the assessment of liver fibrosis in patients with iron overload, using transient elastography (TE) as reference standard.METHODSSixty-seven consecutive patients with MRI detectable iron overload (T2*<6.3 ms) were enrolled. TE and RTE were performed on the same day as MRI. Elastograms were acquired by an experienced operator and analyzed by calculating the elastic ratio between perihepatic soft tissues and liver parenchyma. An elliptical ROI of 1cm(2) (Z1) was positioned in the liver parenchyma and a smaller elliptical ROI of 2mm(2) (Z2) was positioned in a homogeneously soft (red) region of the diaphragm, which was considered as internal control to calculate the elastic ratio Z2/Z1.RESULTSSeven patients were excluded because of invalid TE or RTE examinations. The remaining 60 patients were 57% males and 43% females (mean age: 42 [21-76] years), including 37 homozygous-β-thalassemics, 13 patients with β-thalassemia intermedia, 6 with primary hemochromatosis, and 4 with myelodysplastic syndrome. Increasing elastic ratios were significantly correlated with increasing TE values (r=0.645, 95% CI 0.468-0.772, P<0.0001). The mean elastic ratios for each METAVIR group were as follows: F0/1 = 1.9 ± 0.4; F2 = 2.2 ± 0.4; F3 = 2.9 ± 0.5; F4 = 3.2 ± 0.4. The diagnostic accuracy of RTE for F ≥ 2 evaluated by AUC-ROC analysis was 0.798 (95% CI 0.674-0.890). The diagnostic accuracy of RTE for F ≥ 3 was 0.909 (95% CI 0.806-0.968). At a cut-off ≥ 2.75, RTE showed a sensitivity of 70% (95% CI 45.7-88.1) and a specificity of 97.5% (95% CI 86.8-99.9).CONCLUSIONSIn patients with MRI-detectable liver iron-overload RTE allows to discriminate between F0/1-F2 and F3-F4 with a reasonable diagnostic accuracy.