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Application of thyroid hormone and analogue thereof in preparation of drug for treating alpha-thalassemia

A technology for thyroid hormones and thalassemia, which is applied in blood diseases, drug combinations, and medical preparations containing active ingredients, etc., can solve the problems of acute hemolysis, endanger the life safety of mothers and infants, and is difficult to be widely used, so as to achieve widespread promotion and use Effect

Pending Publication Date: 2020-07-10
SHANGHAI SPH RARE DISEASE PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] 1. Blood transfusion can cause serious maternal and infant complications, and lead to iron overload in the patient's body, which in turn causes damage to multiple organs, mainly affecting the heart, liver, pancreas and various endocrine organs, endangering the lives of mothers and infants
[0006] 2. Blood transfusion can cause adverse reactions such as fever, chills, and rashes. In severe cases, it can lead to acute hemolysis, tracheal constriction, and blood pressure drop.
[0007] 3. Blood transfusion may face the risk of infectious diseases through blood
[0008] 4. Intrauterine blood transfusion requires high technical requirements and is difficult to be widely used
[0009] 5. The cost of blood transfusion is high, especially for patients who need life-long blood transfusion, resulting in a huge economic burden
However, so far, no drugs that activate the expression of the ζ-globin gene have emerged

Method used

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  • Application of thyroid hormone and analogue thereof in preparation of drug for treating alpha-thalassemia
  • Application of thyroid hormone and analogue thereof in preparation of drug for treating alpha-thalassemia
  • Application of thyroid hormone and analogue thereof in preparation of drug for treating alpha-thalassemia

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] In K562 cells, Triac specifically activates the expression process of ζ-globin gene (HBZ) as follows:

[0032] During the differentiation process of K562 cells, after they were treated with hemin or hemin+Triac for 72 hours, the cells were collected by centrifugation at 2000rpm for 5 minutes, the total RNA was extracted using TRIzol reagent (Invitrogen), and then the reverse transcription kit (ReverTra Ace, TOYOBO) was used Synthesize cDNA, and finally use SYBRGreen Realtime PCR Master Mix (TOYOBO) reagent for quantitative PCR to detect gene expression level.

[0033] The quantitative PCR reaction system is:

[0034]

[0035]

[0036] The quantitative PCR reaction conditions are:

[0037] Hot start: 95°C, 10 minutes;

[0038] Denaturation: 95°C, 10 seconds;

[0039] Annealing / extension: 60°C, 30 seconds.

[0040] 40 loops.

[0041] Melting curve analysis.

[0042] Such as figure 1 As shown, after K562 was treated with Triac for 72 hours, quantitative PCR re...

Embodiment 2

[0056] During the development of zebrafish embryos, Triac, T3, and T4 were added to zebrafish embryos 96 hours after fertilization. After being treated with Triac, T3, and T4 for 24 hours, the embryos were fixed with 4% paraformaldehyde and tested by whole-embryo in situ hybridization. Technique detection ζ-globin gene (hbae5) expression.

[0057] Such as figure 2 As shown, in zebrafish embryos, Triac, T3 and T4 significantly activated the expression of ζ-globin gene (hbae5), that is, significantly upregulated.

Embodiment 3

[0059] During the development of zebrafish embryos, Triac, T3, and T4 were added to zebrafish embryos 96 hours after fertilization. After 24 hours of treatment, the embryos were collected, and total RNA was extracted using TRIzol reagent (Invitrogen), and then reverse transcription kit (ReverTra Ace, TOYOBO) to synthesize cDNA, and finally use SYBRGreen Realtime PCR Master Mix (TOYOBO) reagent for quantitative PCR to detect gene expression level.

[0060] The quantitative PCR reaction system is:

[0061]

[0062] The quantitative PCR reaction conditions are:

[0063] Hot start: 95°C, 10 minutes;

[0064] Denaturation: 95°C, 10 seconds;

[0065] Annealing / extension: 60°C, 30 seconds.

[0066] 40 loops.

[0067] Melting curve analysis.

[0068] Such as image 3 As shown, in zebrafish embryos, Triac, T3 and T4 significantly activated the expression of the ζ-globin gene (hbae5), that is, quantitative PCR results showed that the expression of the ζ-globin gene (hbae5) was ...

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Abstract

The invention provides an application of thyroid hormone and an analogue thereof in preparation of a drug for treating alpha-thalassemia. The thyroid hormone and the analogue can be specifically applied in regulation of expression of zeta-globin genes, in the differentiation process of K562 cells, the thyroid hormone analogue can be specifically and significantly up-regulate the expression of thezeta-globin gene (HBZ) by up to 50 times, and in model animal zebrafish embryos, after treatment is performed by using the thyroid hormone and the analogue, the expression of the zeta-globin gene (hbae5) can also be specifically up-regulated by up to 30-70 times; therefore, the thyroid hormone and the analogue thereof can be used to specifically activate the expression of the zeta-globin genes, that is, to reactivate the silent zeta-globin genes in patients with the alpha-thalassemia to inhibit destruction of red blood cells, the thyroid hormone and the analogue realizes a method for preparingthe drug for treating the alpha-thalassemia, the economical, safe and effective method is provided for treatment of the alpha-thalassemia, and the method can be widely promoted and used.

Description

technical field [0001] The invention belongs to the technical field of thalassemia, and specifically relates to the application of thyroid hormone and its analogs in the preparation and treatment of α-thalassemia. Background technique [0002] Thalassemia is one of the most common single-gene genetic diseases that have a great impact on human health worldwide. The etiology is hemolytic anemia caused by the deletion or mutation of the globin gene (globin) leading to the disorder of globin chain synthesis, which causes the imbalance of hemoglobin (hemoglobin) composition ratio, and finally leads to the destruction of red blood cells. Classified according to the type of globin chain involved, the most common are alpha-thalassemia and beta-thalassemia. Decreased α-globin synthesis is α-thalassemia and decreased β-globin synthesis is β-thalassemia. Although the number of α-thalassemia gene carriers is higher than that of β-thalassemia, and the number of patients with α-thalasse...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/198A61P7/06
CPCA61K31/198A61P7/06A61K31/192
Inventor 袁浩朱军
Owner SHANGHAI SPH RARE DISEASE PHARMA CO LTD
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