COMPOSITION FOR TREATMENT OF KELOID SYSTEMIC SCLEROSIS THROUGH MITOCHONDRIAL TRANSPLANTATION

• Main Authors: CHO, Mi La, LEE, Chae-Rim, JEON, Su Been, CHOI, Jeong Won, LEE, A Ram, LEE, Jung-Ho, LEE, Seon Yeong
• Format: Patent
• Language: English; French; Korean
• Published: 02.05.2024
• Subjects: FOODS OR FOODSTUFFS; FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BYSUBCLASSES A23B - A23J; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OFNUTRITIVE QUALITIES, PHYSICAL TREATMENT; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES

The present invention relates to a composition for treatment of mitochondrial transplantation for immunomodulation and fibrosis control in multiple sclerosis. The present invention confirmed that, when muscle-derived mitochondria are transplanted into an animal model with multiple sclerosis, disease activity of multiple sclerosis is decreased, mitochondrial dysfunction is ameliorated, and autoimmune-related immune cells are controlled. Also, it was confirmed that, in the animal model with multiple sclerosis, mitochondrial transplantation increases a variety of intestinal bacterial flora, increases the phylum Firmicutes which are beneficial bacteria, decreases the phylum Bacterodites which are harmful bacteria, and increases, at the level of the genus, the genera Akkermansia and Romboutsia, thereby regulating the homeostasis of the intestinal bacterial flora. It was confirmed that mitochondrial transplantation reduces the expression of inflammatory fibrosis factors in keloid patient-derived fibroblasts. Also, it was confirmed that, even in cells where fibrosis is accelerated due to IL-17, mitochondrial transplantation reduces the expression of inflammatory fibrosis factors and induces autophage-activating factors, thereby ameliorating keloids. Also, it was confirmed that, in a keloid patient-derived avatar animal model, mitochondrial transplantation inhibits fibrosis of new tissue. Also, it was confirmed that, in vimentin-immunized systemic sclerosis, mitochondrial transplantation inhibits the expression of autoantibodies and inhibits tissue fibrosis. La présente invention concerne une composition pour le traitement de la transplantation mitochondriale pour l'immunomodulation et le contrôle de la fibrose dans la sclérose en plaques. La présente invention a confirmé que, lorsque des mitochondries issues de muscle sont transplantées dans un modèle animal atteint de sclérose en plaques, l'activité de la maladie de sclérose en plaques est réduite, le dysfonctionnement mitochondrial est amélioré, et les cellules immunitaires associées à l'auto-immunité sont contrôlées. Il a également été confirmé que, dans le modèle animal de la sclérose en plaques, la transplantation mitochondriale augmente la variété de la flore bactérienne intestinale, augmente les phylum Firmicutes qui sont des bactéries bénéfiques, diminue les phylum Bacterodites qui sont des bactéries nuisibles, et augmente, au niveau du genre, les genres Akkermansia et Romboutsia, régulant ainsi l'homéostasie de la flore bactérienne intestinale. Il a été confirmé que la transplantation mitochondriale réduit l'expression des facteurs de fibrose inflammatoire dans les fibroblastes issus d'un patient chéloïde. Il a également été confirmé que, même dans les cellules où la fibrose est accélérée par l'IL-17, la transplantation mitochondriale réduit l'expression des facteurs de fibrose inflammatoire et induit des facteurs d'activation de l'autophagie, ce qui permet d'améliorer les chéloïdes. En outre, il a été confirmé que, dans un modèle animal avatar issu d'un patient chéloïde, la transplantation mitochondriale inhibe la fibrose de nouveau tissu. De plus, il a été confirmé que, dans la sclérose systémique immunisée par la vimentine, la transplantation mitochondriale inhibe l'expression des auto-anticorps et inhibe la fibrose tissulaire. 본 발명은 다발성경화증 면역조절과 섬유화 제어를 위한 미토콘드리아 이식 치료 조성물에 관한 것으로서, 본 발명은 다발성 경화증 동물모델에 근육 유래 미토콘드리아를 이식하면, 다발성경화증의 병증 활성도가 감소하고, 미토콘드리아 기능이상이 개선되며, 자가면역 관련 면역세포가 조절되는 것을 확인하였다. 또한 미토콘드리아의 이식이 다발성 경화증 동물모델에서, 장내 균총의 다양성을 증가시키고, 유익균인 Firmicutes 문을 증가시키고, 유해균인 Bacterodites 문을 감소시키며, 속 수준에서 Akkermansia 및 Romboutsia 속을 증가시키켜, 장내 균총의 항상성을 조절하는 것을 확인하였다. 미토콘드리아의 이식이, 켈로이드 환자 유래의 섬유아세포에서, 염증성 섬유화 인자의 발현을 감소시키는 것을 확인하였다. 또한, IL-17로 섬유화가 가속화된 세포에서도, 염증성 섬유화 인자의 발현을 감소시키고, 오토파지 활성화 인자를 유도하여, 켈로이드를 개선시키는 것을 확인하였다. 또한, 켈로이드 환자 아바타 동물모델에서, 신조직의 섬유화를 억제시키는 것을 확인하였다. 또한, 비멘틴 면역화 전신경화증에서, 자가 항체의 발현을 억제하고, 조직 섬유화를 억제하는 것을 확인하였다.