【紹介報告】
Comparison between administration routes in brain distribution and drug efficacy of ASO (ICV vs IT)
Sano et al., Poster P2-41, The 8th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan, 2023
https://www.axcelead.com/wp-content/uploads/2023/07/8_kakusangakkai_j.pdf
【発表概要】
今回のサイエンスカフェではマウスを用いた脳室内投与と髄腔内投与の比較について発表します。
Antisense oligonucleotide (ASO) を用いて中枢神経を標的とする場合、多くのASOは血液脳関門を通過できないため、脳室内 (intracerebroventricular; ICV) 投与や髄腔内(intrathecal; IT) 投与といった中枢神経系へ直接暴露させる投与ルートが選択される。臨床適応では侵襲性の低いIT投与が選択されることが多いが、実験動物、特にマウスにおいてはICVが汎用され、IT投与後のASOの脳内分布、暴露量および作用を評価した報告は少ない。そこで、我々はマウスにおける堅牢なIT投与法を構築し、投与ルートの違いによる体内動態やknockdown効率 の相違について評価したので紹介する。
【Summary】
In this Science Café, I will present a comparison between intracerebroventricular (ICV) and intrathecal (IT) administration using mice.
When targeting the central nervous system with antisense oligonucleotides (ASO), many ASOs cannot penetrate the blood-brain barrier. Therefore, routes of administration such as ICV and IT are chosen to directly expose the central nervous system. In clinical, less invasive IT administration is often preferred. However, in experimental animals, especially mice, ICV is commonly used. and there are few reports evaluating the brain distribution, exposure, and effects of ASO after IT administration. I will introduce that a robust IT administration method and investigations of the differences in pharmacokinetics and knockdown of ASO for each administration routes in mice.
(2024.2.29 Shonan iPark Science Cafe 170th)
