Title:
ANIMAL MODEL OF CHARCOT-MARIE-TOOTH DISEASE
Document Type and Number:
WIPO Patent Application WO/2024/029755
Kind Code:
A1
Abstract:
The present invention relates to an animal model of Charcot-Marie-Tooth disease caused by K141N or K141T mutations in HSPB8. In this animal model expressing the K141N or K141T mutant HSPB8 protein, symptoms of Charcot-Marie-Tooth disease, such as motor deficit, mitochondrial dysfunction, and reduced levels of mitophagy, were observed, confirming that Charcot-Marie-Tooth disease can be induced by K141N or K141T mutations in the HSPB8 protein. Therefore, the animal model expressing the K141N or K141T mutant HSPB8 protein can be used as an animal model of Charcot-Marie-Tooth disease. The symptoms of Charcot-Marie-Tooth disease were significantly reduced by the expression and activation of PINK1 or Parkin, so that the animal model can be used in therapeutic applications for Charcot-Marie-Tooth disease.
Inventors:
KOH HYONGJONG (KR)
KANG KYONG-HWA (KR)
HAN JI EUN (KR)
KANG KYONG-HWA (KR)
HAN JI EUN (KR)
Application Number:
PCT/KR2023/009373
Publication Date:
February 08, 2024
Filing Date:
July 04, 2023
Export Citation:
Assignee:
UNIV DONG A RES FOUND FOR IND ACAD COOP (KR)
International Classes:
C12Q1/6883; A01K67/033; A61K38/45; A61P21/00; A61P25/02; G01N33/68
Domestic Patent References:
| WO2019068865A1 | 2019-04-11 |
Foreign References:
| US20070101447A1 | 2007-05-03 |
Other References:
NAKHRO KHRIEZHANUO, PARK JIN-MO, KIM YE JIN, YOON BO RAM, YOO JEONG HYUN, KOO HEASOO, CHOI BYUNG-OK, CHUNG KI WHA: "A novel Lys141Thr mutation in small heat shock protein 22 (HSPB8) gene in Charcot–Marie–Tooth disease type 2L", NEUROMUSCULAR DISORDERS, ELSEVIER LTD, GB, vol. 23, no. 8, 1 August 2013 (2013-08-01), GB , pages 656 - 663, XP093136646, ISSN: 0960-8966, DOI: 10.1016/j.nmd.2013.05.009
MILLER SILKE; MUQIT MIRATUL M.K.: "Therapeutic approaches to enhance PINK1/Parkin mediated mitophagy for the treatment of Parkinson’s disease", NEUROSCIENCE LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 705, 1 January 1900 (1900-01-01), AMSTERDAM, NL , pages 7 - 13, XP085708649, ISSN: 0304-3940, DOI: 10.1016/j.neulet.2019.04.029
STORKEBAUM ERIK, LEITÃO-GONÇALVES RICARDO, GODENSCHWEGE TANJA, NANGLE LESLIE, MEJIA MONICA, BOSMANS INGE, OOMS TINNE, JACOBS AN, V: "Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot–Marie–Tooth neuropathy", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 106, no. 28, 14 July 2009 (2009-07-14), pages 11782 - 11787, XP093136650, ISSN: 0027-8424, DOI: 10.1073/pnas.0905339106
KANG KYONG-HWA, HAN JI EUN, KIM HYUNJIN, KIM SOHEE, HONG YOUNG BIN, YUN JEANHO, NAM SOO HYUN, CHOI BYUNG-OK, KOH HYONGJONG: "PINK1 and Parkin Ameliorate the Loss of Motor Activity and Mitochondrial Dysfunction Induced by Peripheral Neuropathy-Associated HSPB8 Mutants in Drosophila Models", BIOMEDICINES, MDPI, BASEL, vol. 11, no. 3, Basel , pages 832, XP093127990, ISSN: 2227-9059, DOI: 10.3390/biomedicines11030832
HAN, J. E. ET AL.: "Small heat shock protein HSPB8 mutation recapitulates features of Charcot-Marie-Tooth disease (CMT) accompanying with mitochondria dysfunction in Drosophila", THE 51ST ANNUAL MEETING OF KOREAN DROSOPHILA SOCIETY, poster-44, 4 July 2022 (2022-07-04)
MILLER SILKE; MUQIT MIRATUL M.K.: "Therapeutic approaches to enhance PINK1/Parkin mediated mitophagy for the treatment of Parkinson’s disease", NEUROSCIENCE LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 705, 1 January 1900 (1900-01-01), AMSTERDAM, NL , pages 7 - 13, XP085708649, ISSN: 0304-3940, DOI: 10.1016/j.neulet.2019.04.029
STORKEBAUM ERIK, LEITÃO-GONÇALVES RICARDO, GODENSCHWEGE TANJA, NANGLE LESLIE, MEJIA MONICA, BOSMANS INGE, OOMS TINNE, JACOBS AN, V: "Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot–Marie–Tooth neuropathy", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 106, no. 28, 14 July 2009 (2009-07-14), pages 11782 - 11787, XP093136650, ISSN: 0027-8424, DOI: 10.1073/pnas.0905339106
KANG KYONG-HWA, HAN JI EUN, KIM HYUNJIN, KIM SOHEE, HONG YOUNG BIN, YUN JEANHO, NAM SOO HYUN, CHOI BYUNG-OK, KOH HYONGJONG: "PINK1 and Parkin Ameliorate the Loss of Motor Activity and Mitochondrial Dysfunction Induced by Peripheral Neuropathy-Associated HSPB8 Mutants in Drosophila Models", BIOMEDICINES, MDPI, BASEL, vol. 11, no. 3, Basel , pages 832, XP093127990, ISSN: 2227-9059, DOI: 10.3390/biomedicines11030832
HAN, J. E. ET AL.: "Small heat shock protein HSPB8 mutation recapitulates features of Charcot-Marie-Tooth disease (CMT) accompanying with mitochondria dysfunction in Drosophila", THE 51ST ANNUAL MEETING OF KOREAN DROSOPHILA SOCIETY, poster-44, 4 July 2022 (2022-07-04)
Attorney, Agent or Firm:
WIE, Byoung-Gap (KR)
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