JP6108633B2 - Kcnq1遺伝子の多型に基づいた治療方法 - Google Patents
Kcnq1遺伝子の多型に基づいた治療方法 Download PDFInfo
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- JP6108633B2 JP6108633B2 JP2015093382A JP2015093382A JP6108633B2 JP 6108633 B2 JP6108633 B2 JP 6108633B2 JP 2015093382 A JP2015093382 A JP 2015093382A JP 2015093382 A JP2015093382 A JP 2015093382A JP 6108633 B2 JP6108633 B2 JP 6108633B2
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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Description
本出願は、これによって本明細書に組み込まれる2009年4月6日出願の同時係属の米国特許仮出願第61/167,136号の利益を主張する。
[技術分野]
本発明は、概して、抗精神病薬を投与すること、より具体的には、個体のKCNQ1遺伝子型に基づいて抗精神病薬を投与することに関する。
心電図のQT間隔の延長(Q波の始めからT波の終わりまでの間の時間)は、QT延長症候群(LQTS)と称される。LQTSは遺伝要素を含む可能性がある。一部のLQTS患者では、QT延長は慢性的な状態になり得る。一部の人では、LQTSはQT間隔を延長する活性医薬成分の投与によって誘発され得る。
本発明は、QTc間隔を延長する能力がある化合物を投与するための方法及び個体がそのようなQTc延長の素因を持つかどうかを予測するための方法を提供する。
上に示したように、本発明は、抗精神病薬を個体のKCNQ1遺伝子型に基づいて投与するための方法を提供する。
Claims (15)
- 個体が、活性医薬成分投与後のQTc間隔の延長の素因を持つかどうかを決定する方法であって、前記個体のKCNQ1遺伝子型の少なくとも一部を決定するステップを含み、
決定するステップが、参照配列AJ006345.1の79764位、参照配列AJ006345.1の286414位、参照配列AJ006345.1の78927位、及び参照配列AJ006345.1の2483474位からなる群から選択される少なくとも1つの一塩基多型(SNP)遺伝子座における個体のKCNQ1遺伝子型を決定するサブステップを含み、
前記活性医薬成分が、イロペリドン又は1−[4−[3−[4−(6−フルオロ−1,2−ベンゾイソオキサゾール−3−イル)−1−ピペリジニル]プロポキシ]−3−メトキシフェニル]エタノールである、方法。 - 個体のKCNQ1遺伝子型が、
参照配列AJ006345.1の79764位におけるGGを含む場合に、個体がQTc間隔の延長の素因を持つと結論付けるステップをさらに含む、請求項1に記載の方法。 - 個体のKCNQ1遺伝子型が、
参照配列AJ006345.1の286414位におけるAAを含む場合に、個体がQTc間隔の延長の素因を持つと結論付けるステップをさらに含む、請求項1に記載の方法。 - 個体のKCNQ1遺伝子型が、
参照配列AJ006345.1の78927位におけるCCを含む場合に、個体がQTc間隔の延長の素因を持つと結論付けるステップをさらに含む、請求項1に記載の方法。 - 個体のKCNQ1遺伝子型が、
参照配列AJ006345.1の2483474位におけるTTを含む場合に、個体がQTc間隔の延長の素因を持つと結論付けるステップをさらに含む、請求項1に記載の方法。 - 個体のCYP2D6遺伝子型の少なくとも一部を決定するステップをさらに含む、請求項1〜5のいずれか一項に記載の方法。
- 個体のCYP2D6遺伝子型の少なくとも一部を決定するステップが、個体のCYP2D6遺伝子配列がCYP2D6G1846A多型を含むかどうかを決定するサブステップを含む、請求項6に記載の方法。
- 個体のCYP2D6遺伝子型の少なくとも一部を決定するステップが、個体のCYP2D6遺伝子配列がCYP2D6C100T多型を含むかどうかを決定するサブステップを含む、請求項6に記載の方法。
- 個体のKCNQ1遺伝子型の少なくとも一部を決定するステップが、個体のKCNQ1遺伝子の発現産物を特徴づけるサブステップを含む、請求項1に記載の方法。
- 患者が、化合物を投与されることによるQT間隔の延長の危険性を有するかどうかを決定する方法であって、
前記化合物がイロペリドン又は1−[4−[3−[4−(6−フルオロ−1,2−ベンゾイソオキサゾール−3−イル)−1−ピペリジニル]プロポキシ]−3−メトキシフェニル]エタノールであり、
患者のKCNQ1遺伝子型を決定するステップを含み、
前記患者のKCNQ1遺伝子型が、参照配列AJ006345.1の79764位におけるGG KCNQ1遺伝子型、参照配列AJ006345.1の286414位におけるAA KCNQ1遺伝子型、参照配列AJ006345.1の78927位におけるCC KCNQ1遺伝子型、又は参照配列AJ006345.1の2483474位におけるTT KCNQ1遺伝子型である場合、患者が化合物の投与によるQT間隔の延長の危険性を有する、方法。 - 患者のKCNQ1遺伝子型を決定するステップが、患者のKCNQ1遺伝子の発現産物を特徴づけるサブステップを含む、請求項10に記載の方法。
- 患者のCYP2D6遺伝子の発現産物を特徴づけるステップをさらに含む、請求項10に記載の方法。
- 特徴づけられた発現産物が、CYP2D6G1846A及びCYP2D6C100Tからなる群から選択されるCYP2D6多型に対応するかどうかを決定するステップをさらに含む、請求項12に記載の方法。
- 化合物が、イロペリドンである、請求項10〜13のいずれか一項に記載の方法。
- 患者に投与する活性医薬成分の有効量を決定する方法であって、
参照配列AJ006345.1の286414位又は参照配列AJ006345.1の2483474位における患者のKCNQ1遺伝子型を決定するステップと、
患者の286414位又は2483474位のKCNQ1遺伝子型がQT延長の危険性の上昇に関連するかどうかを決定するステップと、
患者のKCNQ1遺伝子型の286414位がAA又は2483474位がTTである場合に、患者のKCNQ1遺伝子型がQT延長の危険性の上昇に関連すると決定し、前記活性医薬成分の有効な量を、QT延長の危険性の上昇に関連しないKCNQ1遺伝子型を有する個体に有効な前記活性医薬成分の量よりも少ない量に決定するステップと、を含み、
前記活性医薬成分がイロペリドン又は1−[4−[3−[4−(6−フルオロ−1,2−ベンゾイソオキサゾール−3−イル)−1−ピペリジニル]プロポキシ]−3−メトキシフェニル]エタノールである、方法。
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