JP5391401B2 - 中枢神経髄鞘形成不全の治療用組成物および中枢神経髄鞘形成不全の治療剤 - Google Patents
中枢神経髄鞘形成不全の治療用組成物および中枢神経髄鞘形成不全の治療剤 Download PDFInfo
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- JP5391401B2 JP5391401B2 JP2008208155A JP2008208155A JP5391401B2 JP 5391401 B2 JP5391401 B2 JP 5391401B2 JP 2008208155 A JP2008208155 A JP 2008208155A JP 2008208155 A JP2008208155 A JP 2008208155A JP 5391401 B2 JP5391401 B2 JP 5391401B2
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Description
Duncan ID, Journal of the Neurological Science, 228: 204-205 (2005) Inoue K, Neurogenetics, 6 (1): 1-16 (2005)
本発明に係る、PLP1タンパク質の機能亢進によって生じる中枢神経髄鞘形成不全治療用組成物は、MAPK経路活性化を阻害するための阻害物質のいずれか、もしくは、それらのうち2つ以上の組み合わせを含有することを特徴とする。この阻害物質は、MAPK経路の因子(例えば、K-Ras、H-Ras、N-Ras、A-Raf、B-Raf、c-Raf、MAPKK、MAPK、など)の活性を阻害することにより、MAPKの活性を阻害する物質であれば制限はなく、その物質は、低分子化合物やドミナントネガティブ型タンパク質変異体などであってもよいが、MAPKK活性阻害物質であることが好ましく、U0126(1,4-Diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene)またはPD98059(2′-Amino-3′-methoxyflavone)であることがさらに好ましい。
前記中枢神経髄鞘形成不全治療組成物のいずれか、もしくはそれらのうち2つ以上の組み合わせは、当業者に周知の薬学的に許容される担体、希釈剤、腑形剤等の製剤用添加物を用いて剤形化することができる。その形態は治療に適切な剤形であれば特に特定されず、例えば、経口剤として、錠剤、カプセル、顆粒、散剤、シロップ、腸溶剤、徐放性カプセル、カシュー、咀嚼錠、ドロップ、丸剤、内用液剤、菓子錠剤、徐放錠、徐放性顆粒等に剤形化してもよい。また、注射剤に剤形化してもよく、例えば、溶液性注射剤、乳濁性注射剤、または固形注射剤等が挙げられる。本治療剤には、上記製剤用添加物の他、異なる医薬組成物を配合することもできる。
なお、中枢神経髄鞘形成不全治療剤の患者への投与方法および投与量は、投与目的、剤形、患者の状態などに応じ、当業者が適宜選択可能である。
本実施例では、まず、PLP1タンパク質の機能亢進によって中枢神経において髄鞘が形成不全になる疾患のモデルとして、PLP1を過剰発現させることで、髄鞘形成不全を起こすオリゴデンドロサイトを作製した。
プライマーS: ccgggatccatgggcttgttagagtgctgtgcaagatgtctg (配列番号1)
プライマーAS: ccgggatcctcagaacttggtgcctcggcccatg (配列番号2)
次に、MAPKK活性阻害剤によって、この髄鞘形成不全症状が正常レベルまで改善されることを示す。
Claims (2)
- PLP1タンパク質の機能亢進によって生じる中枢神経髄鞘形成不全の治療用組成物であって、
MAPK経路活性化を阻害するための阻害物質を含有し、
前記阻害物質が、U0126および/またはPD98059であることを特徴とする、治療用組成物。 - 請求項1に記載の治療用組成物を含有する、中枢神経髄鞘形成不全の治療剤。
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JP2008208155A JP5391401B2 (ja) | 2008-08-12 | 2008-08-12 | 中枢神経髄鞘形成不全の治療用組成物および中枢神経髄鞘形成不全の治療剤 |
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JP2008208155A JP5391401B2 (ja) | 2008-08-12 | 2008-08-12 | 中枢神経髄鞘形成不全の治療用組成物および中枢神経髄鞘形成不全の治療剤 |
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JP5391401B2 true JP5391401B2 (ja) | 2014-01-15 |
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EP4276187A3 (en) * | 2016-12-08 | 2024-01-17 | Case Western Reserve University | Methods and compositions for enhancing functional myelin production |
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US20050175998A1 (en) * | 2001-07-30 | 2005-08-11 | Jin Nakahara | Medicinal compositions containing fc receptor gamma-chain activator |
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