Title:
APPLICATION OF THYROID HORMONE AND ANALOGUE THEREOF IN PREPARATION OF DRUG FOR TREATING SICKLE-CELL DISEASE
Document Type and Number:
WIPO Patent Application WO/2021/208551
Kind Code:
A1
Abstract:
An application of thyroid hormone and an analogue thereof in the preparation of a drug for treating sickle-cell disease. Specifically, thyroid hormone and the analogue thereof can be applied in the regulation of the expression of ζ-globin gene. In a K562 cell differentiation process, the thyroid hormone analogue can specifically and significantly up-regulate the expression of ζ-globin gene (HBZ), up to 50 times. After model animal zebrafish embryos are treated with thyroid hormone and the analogue thereof, the expression of ζ-globin gene (hbae5) can also be specifically up-regulated, up to 30-70 times. Thyroid hormone and the analogue thereof can specifically activate the expression of ζ-globin gene, that is, reactivate the silent ζ-globin gene in patients with sickle-cell disease to inhibit sickle hemoglobin S polymerization, so as to become a method for preparing a drug for treating sickle-cell disease. This provides an economical, safe and effective method for the treatment of sickle-cell disease, and can be widely generalized.
Inventors:
YUAN HAO (CN)
Application Number:
PCT/CN2021/072734
Publication Date:
October 21, 2021
Filing Date:
January 19, 2021
Export Citation:
Assignee:
RUIJIN HOSPITAL SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE (CN)
International Classes:
A61K31/198; A61K31/192; A61P7/06
Foreign References:
| CN111419834A | 2020-07-17 |
Other References:
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EBERT BENJAMIN L.; MAK RAYMOND; PRETZ JENNIFER L.; PECK DAVID; HAGGERTY STEPHEN; TOLLIDAY NICOLA; GOLUB TODD R.: "High Throughput Screen To Identify Small Molecules That Differentially Regulate Expression of the Globin Genes.", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 106, no. 11, 16 November 2005 (2005-11-16), US , pages 3632, XP086675206, ISSN: 0006-4971, DOI: 10.1182/blood.V106.11.3632.3632
FUHR J. E., N. GENGOZIAN, M. OVERTON: "In Vitro Stimulation of Primate Hemoglobin Synthesis by L-Thyroxine", BLOOD, vol. 49, no. 3, 1 March 1977 (1977-03-01), XP055858773, DOI: 10.1182/blood.V49.3.407.407
EVLIYAOGLU NURDAN, YURDANUR KILINC, OZOCUL SARGIN: "Thyroid Functions in Mild and Severe Forms of Sickle Cell Anemia", ACTA PAEDIATRICA JAPONICA, vol. 38, no. 5, 1 October 1996 (1996-10-01), pages 460 - 463, XP055858780, DOI: 10.1111/j.1442-200X.1996.tb03527.x
SOLIMAN ASHRAF T, DE SANCTIS VINCENZO, YASSIN MOHAMED, WAGDY MAGDA, SOLIMAN NADA: "Chronic anemia and thyroid function", ACTA BIO-MEDICA DE L'ATENEO PARMENSE, MATTIOLI 1885, ITALY, 28 April 2017 (2017-04-28), Italy, pages 119 - 127, XP055858784, Retrieved from the Internet DOI: 10.23750/abm.v88i1.6048
EBERT BENJAMIN L.; MAK RAYMOND; PRETZ JENNIFER L.; PECK DAVID; HAGGERTY STEPHEN; TOLLIDAY NICOLA; GOLUB TODD R.: "High Throughput Screen To Identify Small Molecules That Differentially Regulate Expression of the Globin Genes.", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 106, no. 11, 16 November 2005 (2005-11-16), US , pages 3632, XP086675206, ISSN: 0006-4971, DOI: 10.1182/blood.V106.11.3632.3632
FUHR J. E., N. GENGOZIAN, M. OVERTON: "In Vitro Stimulation of Primate Hemoglobin Synthesis by L-Thyroxine", BLOOD, vol. 49, no. 3, 1 March 1977 (1977-03-01), XP055858773, DOI: 10.1182/blood.V49.3.407.407
EVLIYAOGLU NURDAN, YURDANUR KILINC, OZOCUL SARGIN: "Thyroid Functions in Mild and Severe Forms of Sickle Cell Anemia", ACTA PAEDIATRICA JAPONICA, vol. 38, no. 5, 1 October 1996 (1996-10-01), pages 460 - 463, XP055858780, DOI: 10.1111/j.1442-200X.1996.tb03527.x
SOLIMAN ASHRAF T, DE SANCTIS VINCENZO, YASSIN MOHAMED, WAGDY MAGDA, SOLIMAN NADA: "Chronic anemia and thyroid function", ACTA BIO-MEDICA DE L'ATENEO PARMENSE, MATTIOLI 1885, ITALY, 28 April 2017 (2017-04-28), Italy, pages 119 - 127, XP055858784, Retrieved from the Internet
Attorney, Agent or Firm:
SHANGHAI BRIDGE INTELLECTUAL PROPERTY AGENCY CO., LTD. (CN)
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