経鼻投与におけるJAL-TA9の脳内輸送

• Published in: 日本薬理学会年会要旨集 p. 1-B-S19-3
• Main Authors: 幡川, 祐資, 田中, 晶子, 古林, 呂之, 中村, 里菜, 小西, 元美, 秋澤, 俊史, 坂根, 稔康
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: amyloid beta-protein; peptide; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_1-B-S19-3

We have reported on two Catalytides (Catalytic peptides), JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMI). Both peptides belong to the Tob/BTG family proteins and cleave Aβ42 [1, 2]. Although Catalytides must be delivered to the brain parenchyma to treat Alzheimer’s disease, the blood-brain barrier (BBB) limits their entry into the brain from the systemic circulation. Thus, we evaluated the direct route of ANA-TA9 from the nasal cavity to the brain to bypass the BBB [3]. In this study, we present our findings on JAL-TA9. Animal studies using rats and mice clarified that the plasma clearance of JAL-TA9 was more rapid than its in vitro degradation in plasma, whole blood, and cerebrospinal fluid (CSF). After nasal administration of JAL-TA9, brain concentrations were significantly higher than after intraperitoneal administration, despite much lower plasma concentration. This observation strongly suggests direct delivery of JAL-TA9 to the brain from the nasal cavity. Similar findings were observed for its transport to CSF after nasal and intravenous administration. The concentration of JAL-TA9 in the olfactory bulb peaked at 5 min, while those in the frontal brain peaked at 30 min and in the occipital brain at 60 min. In conclusion, JAL-TA9 was efficiently delivered to the brain by nasal application compared to other routes.[1] Hatakawa et al., Heliyon, 5, e02454 (2019)[2] Hatakawa et al., Alzheimers Dement. (N Y), 7, e12146 (2021)[3] Hatakawa et al., Pharmaceutics, 13, 1673 (2021).