JP2020536643A - 脳のガンマ振動を同期化する視覚刺激を用いた認知症の治療 - Google Patents
脳のガンマ振動を同期化する視覚刺激を用いた認知症の治療 Download PDFInfo
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Abstract
Description
本出願は、以下の米国仮出願のそれぞれに対する優先権を主張する。2017年10月10日に出願され、「NEUROPROTECTIVE EFFECTS OF COMBINED SENSORY STIMULATION」(代理人整理番号 MITX−9699/00US)という表題の米国仮特許出願第62/570,250号明細書;および2017年10月11日に出願され、「GAMMA ENTRAINMENT BINDS HIGHER ORDER BRAIN REGIONS AND OFFERS NEUROPROTECTION」(代理人整理番号 MITX−0070/00US)という表題の米国仮特許出願第62/570,929号明細書。これらの各仮特許出願明細書は、その全体を参照することにより本明細書に組み込まれる。本出願は、2018年9月19日に出願された「Systems and Methods for Preventing,Mitigating,and/or Treating Dementia」という表題のPCT特許出願番号PCT/US18/51785に対する優先権の利益も主張する。当該出願はその全体で参照により本明細書に組み込まれる。
本発明は、米国国立衛生研究所により与えられたグラント番号RF1 AG054321に基づく米国政府の支援により行われた。米国政府は、本発明において特定の権利を有する。
STAR法
Claims (86)
- その必要のある対象において認知症またはアルツハイマー病を治療するための方法であって、
A)約30Hz〜約50Hzの周波数を有する慢性視覚刺激を前記対象に非侵襲的に送達し、前記対象の少なくとも前頭前野皮質(PFC)および海馬を含む、前記対象の複数の脳領域において同期化ガンマ振動を同調させることを含む、方法。 - A)において、前記慢性視覚刺激が、約35Hz〜約45Hzの周波数を有する、請求項1に記載の方法。
- A)において、前記慢性視覚刺激が、約40Hzの周波数を有する、請求項2に記載の方法。
- A)が、前記対象の少なくとも前頭前野皮質および海馬において約40Hzの局所電場電位(LFP)を誘導することを含む、請求項3に記載の方法。
- A)において、前記慢性視覚刺激が、50%の負荷サイクルを有する、請求項2に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含む、請求項2に記載の方法。
- 前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項6に記載の方法。 - A)が、前記対象の少なくとも前頭前野皮質および海馬において約40Hzの局所電場電位(LFP)を誘導することを含む、請求項7に記載の方法。
- A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項2に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項9に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項10に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項10に記載の方法。 - A)が、前記対象の少なくとも前頭前野皮質および海馬において約40Hzの局所電場電位(LFP)を誘導することを含む、請求項12に記載の方法。
- 前記対象の前記複数の脳領域が、前記対象の視覚皮質、体性感覚皮質、海馬および前頭前野皮質を含む、請求項13に記載の方法。
- A)が、
A1)前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を前記対象に非侵襲的に送達し、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域において同期化ガンマ振動を同時に同調させることを含む、請求項1に記載の方法。 - A1)が、
前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の複数の脳領域間で、30Hz〜50Hzの周波数を有するガンマコヒーレンスを有意に増加させることを含む、請求項15に記載の方法。 - 前記対象の前記複数の脳領域が、前記対象の視覚皮質、体性感覚皮質、海馬および前頭前野皮質を含む、請求項16に記載の方法。
- A)において、前記慢性視覚刺激が、約35Hz〜約45Hzの周波数を有する、請求項17に記載の方法。
- A)において、前記慢性視覚刺激が、約40Hzの周波数を有する、請求項18に記載の方法。
- A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項16に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項20に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項21に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項22に記載の方法。 - A1)がさらに、
A2)前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域間のニューロン活動を変調させることを含む、請求項15に記載の方法。 - A2)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域間のニューロン活動を連動させることを含む、請求項24に記載の方法。 - 前記対象の前記複数の脳領域が、前記対象の視覚皮質、体性感覚皮質、海馬および前頭前野皮質を含む、請求項25に記載の方法。
- A)において、前記慢性視覚刺激が、約35Hz〜約45Hzの周波数を有する、請求項26に記載の方法。
- A)において、前記慢性視覚刺激が、約40Hzの周波数を有する、請求項27に記載の方法。
- A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項24に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項25に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項26に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項27に記載の方法。 - A2)がさらに、
A3)前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の神経変性を低下させることを含む、請求項24に記載の方法。 - A3)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中のアミロイドプラークを低下させることを含む、請求項33に記載の方法。 - A3)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中のタウの過剰リン酸化を低下させることを含む、請求項33に記載の方法。 - A3)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中のニューロンおよびシナプスの減少を低下させることを含む、請求項33に記載の方法。 - A3)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の脳委縮を低下させることを含む、請求項33に記載の方法。 - A3)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の脳室拡張を低下させることを含む、請求項33に記載の方法。 - A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項33に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項39に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項40に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項41に記載の方法。 - A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項34〜38のいずれか1項に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項43に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項44に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項45に記載の方法。 - A2)がさらに、
A3)前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の神経炎症を低下させることを含む、請求項24に記載の方法。 - A3)がさらに、
A4)前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の少なくとも一部のミクログリアの免疫反応を低下させることを含む、請求項47に記載の方法。 - A4)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の前記少なくとも一部のミクログリアを形態変換させることを含む、請求項48に記載の方法。 - A4)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の前記少なくとも一部のミクログリアにおいてタンパク質分解を増加させることを含む、請求項48に記載の方法。 - A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項48に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項51に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項52に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項53に記載の方法。 - A2)がさらに、
前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の膜輸送、細胞内輸送、シナプス機能、神経炎症、アポトーシスプロセス、およびDNA損傷のうちの少なくとも一つに関与する異常改変された遺伝子およびタンパク質を改善することを含む、請求項24に記載の方法。 - A1)がさらに、
A2)前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の学習および記憶を強化することを含む、請求項15に記載の方法。 - A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項56に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項57に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項58に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項59に記載の方法。 - その必要のある対象において認知症またはアルツハイマー病を治療するための方法であって、
A)約30Hz〜約50Hzの周波数を有する慢性視覚刺激を前記対象に非侵襲的に送達し、前記対象の少なくとも前頭前野皮質(PFC)および海馬を含む、前記対象の複数の脳領域において同期化ガンマ振動を同調させることを含み、A)が、前記約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を、前記対象に非侵襲的に送達して、
A1)前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域において同期化ガンマ振動を同時に同調させること、
A2)前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域間のニューロン活動を連動させること、
A3)前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の神経変性を低下させること、
A4)前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の神経炎症を低下させること、
A5)前記対象の少なくとも前頭前野皮質および海馬を含む、前記対象の前記複数の脳領域中の膜輸送、細胞内輸送、シナプス機能、神経炎症、アポトーシスプロセス、およびDNA損傷のうちの少なくとも一つに関与する異常改変された遺伝子およびタンパク質を改善すること、および
A5)前記対象の学習および記憶を強化すること、を含む、方法。 - A)が、前記対象の少なくとも前頭前野皮質および海馬において約40Hzの局所電場電位(LFP)を誘導することを含む、請求項61に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項62に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項63に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項63に記載の方法。 - A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項61に記載の方法。 - その必要のある対象において認知症またはアルツハイマー病を治療するための方法であって、
A)約30Hz〜約50Hzの周波数を有する慢性視覚刺激を前記対象に非侵襲的に送達し、前記対象の複数の脳領域において同期化ガンマ振動を同調させ、前記対象の複数の脳領域において変性ニューロン中の異常改変された遺伝子およびタンパク質を改善することを含む、方法。 - 前記対象の前記複数の脳領域において、前記変性ニューロン中の前記異常改変された遺伝子およびタンパク質が、膜輸送、細胞内輸送、シナプス機能、神経炎症、アポトーシスプロセス、およびDNA損傷のうちの少なくとも一つに関与する、請求項67に記載の方法。
- 前記異常改変された遺伝子およびタンパク質が、前記対象の少なくとも視覚皮質中のNueN−陽性ニューロン核からの遺伝子を含む、請求項68に記載の方法。
- A)が、前記慢性視覚刺激を非侵襲的に送達して、前記対象の少なくとも視覚皮質中のNueN−陽性ニューロン核の減少を低下させる、または割合を維持することを含む、請求項69に記載の方法。
- 前記異常改変された遺伝子およびタンパク質が、S/Tリン酸化タンパク質を含み、A)が、前記慢性視覚刺激を非侵襲的に送達して、前記S/Tリン酸化タンパク質を改変し、前記対象の少なくとも視覚皮質中のS/Tリン酸化を低下させることを含む、請求項68に記載の方法。
- 前記S/Tリン酸化タンパク質が、ダイナミン1(DNM−1)を含み、A)が、前記慢性視覚刺激を非侵襲的に送達して、DNM−1中のSer774リン酸化を低下させることを含む、請求項71に記載の方法。
- 前記異常改変された遺伝子およびタンパク質が、有意に集積が低下した小胞グルタミン酸トランスポーター1(vGlut1)を含み、A)が、前記慢性視覚刺激を非侵襲的に送達して、前記対象の前記複数の脳領域においてvGlut1集積を有意に増加させることを含む、請求項68に記載の方法。
- 前記対象の前記複数の脳領域が、前記対象の視覚皮質、体性感覚皮質、海馬および前頭前野皮質を含む、請求項73に記載の方法。
- A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項67に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項75に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項76に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項77に記載の方法。 - その必要のある対象において認知症またはアルツハイマー病を治療するための方法であって、
A)約30Hz〜約50Hzの周波数を有する慢性視覚刺激を前記対象に非侵襲的に送達し、前記対象の複数の脳領域において同期化ガンマ振動を同時に同調させ、前記対象の前記複数の脳領域の間で、前記30Hz〜50Hzの周波数を有するガンマコヒーレンスを有意に増加させることを含む、方法。 - 前記対象の前記複数の脳領域が、前記対象の視覚皮質、体性感覚皮質、海馬および前頭前野皮質を含む、請求項79に記載の方法。
- A)が、前記対象の少なくとも前頭前野皮質および海馬において約40Hzの局所電場電位(LFP)を誘導することを含む、請求項80に記載の方法。
- A)が、7日よりも長く、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項79に記載の方法。
- A)が、少なくとも22日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項82に記載の方法。
- A)が、少なくとも42日間、少なくとも1日あたり1時間、前記慢性視覚刺激を非侵襲的に送達することを含む、請求項83に記載の方法。
- A)が、矩形波電流シグナルを伴う発光ダイオード(LED)のアレイを駆動させ、前記慢性視覚刺激を生成することを含み、
前記矩形波電流シグナルが、50%負荷サイクルを有し、および
前記矩形波電流シグナルの周波数が、40Hzと等しいか、またはおよそ40Hzである、請求項84に記載の方法。 - A1)がさらに、
約30Hz〜約50Hzの周波数を有する前記慢性視覚刺激を非侵襲的に送達して、前記対象の前記複数の脳領域間のニューロン活動を連動させることを含む、請求項85に記載の方法。
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