JP2018502838A - 新規の再生治療剤としてのcamkk1 - Google Patents
新規の再生治療剤としてのcamkk1 Download PDFInfo
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- JP2018502838A JP2018502838A JP2017530094A JP2017530094A JP2018502838A JP 2018502838 A JP2018502838 A JP 2018502838A JP 2017530094 A JP2017530094 A JP 2017530094A JP 2017530094 A JP2017530094 A JP 2017530094A JP 2018502838 A JP2018502838 A JP 2018502838A
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Abstract
Description
本出願は、2014年12月1日付けで出願された米国仮出願第62/086,026号の優先権を主張し、その開示は参照によりその全体が組み入れられる。
− マッソントリクローム染色によって測定した場合、梗塞のサイズおよび心筋線維化の減少;
− 梗塞部の境界ゾーンにおける血管密度の増加
をもたらしたことが実証された。
本明細書で開示されたように、CAMKK1は、MSC機能の主要な制御因子であることが同定された。SDF−1:CXCR4軸およびCAMKK1が、誘導された発現に関して分子のオーバーラップがないという事実により、CAMKK1およびSDF−1の組合せが、最も明白には急性傷害において相乗効果を有するはずであることが予想され、慢性の組織傷害においてもその可能性があることを示唆する。
以下の実施形態の列挙は、以前の記載を置き換えたりまたはそれらに優先したりするのではなく、それらを補完するためのものであることが意図される。
実施形態1.患者の臓器または組織における虚血または炎症状態を処置する方法であって、該臓器または組織におけるCAMKK1のレベルの増加を誘導することを含む、方法。
実施形態2.前記臓器または組織が、心臓、肝臓、腎臓、脳、脊椎、肺、小腸、大腸、動脈、関節、軟骨、皮膚、またはそれらのあらゆる組合せである、実施形態1に記載の方法。
実施形態3.前記臓器または組織が、心臓または心筋である、実施形態2に記載の方法。
実施形態4.前記臓器または組織におけるCAMKK1のレベルの増加が、CAMKK1タンパク質を前記臓器または組織に投与することによって達成される、前述の実施形態のいずれか一つに記載の方法。
実施形態5.前記臓器または組織におけるCAMKK1のレベルの増加が、CAMKK1をコードする核酸を含むベクターを前記臓器または組織に投与することによって達成される、前述の実施形態のいずれか一つに記載の方法。
実施形態6.ベクターが、プラスミドまたはウイルスベクターである、実施形態5に記載の方法。
実施形態7.前記臓器または組織におけるCAMKK1のレベルの増加が、増加したレベルのCAMKK1を生産するように改変された細胞を投与することによって達成される、前述の実施形態のいずれか一つに記載の方法。
実施形態8.前記臓器または組織におけるCAMKK1のレベルの増加が、CAMKK1のレベルの増加がもたらされるように改変された細胞の培養物からの馴化培地を投与することによって達成される、前述の実施形態のいずれか一つに記載の方法。
実施形態9.細胞が、CAMKK1をコードする核酸を含むベクターで改変された、実施形態7または8に記載の方法。
実施形態10.ベクターが、プラスミドまたはウイルスベクターを含む、実施形態9に記載の方法。
実施形態11.細胞が、CAMKK1の発現を誘導する薬剤で改変された、実施形態7または8に記載の方法。
実施形態12.薬剤が、TGF−β、miR145、Dab2阻害剤、またはそれらのあらゆる組合せである、実施形態11に記載の方法。
実施形態13.Dab2阻害剤が、Dab2のsiRNAである、実施形態12に記載の方法。
実施形態14.CAMKK1が、構成的に活性なCAMKK1である、前述の実施形態のいずれか一つに記載の方法。
実施形態15.構成的に活性なCAMKK1が、CAMKK1 1−413トランケート型を含む、実施形態14に記載の方法。
実施形態16.構成的に活性なCAMKK1が、T108A突然変異CAMKK1、S459A突然変異CAMKK1、またはT108A/S459A突然変異CAMKK1を含む、実施形態14に記載の方法。
実施形態17.タンパク質、ベクター、細胞、または馴化培地が、全身投与されるか、虚血もしくは炎症を起こした組織に直接投与されるか、または虚血もしくは炎症を起こした組織の周辺に投与される、前述の実施形態のいずれか一つに記載の方法。
実施形態18.細胞が、間葉系幹細胞である、前述の実施形態のいずれか一つに記載の方法。
実施形態19.虚血または炎症状態が、急性心筋梗塞、心不全、末梢動脈疾患、卒中、肝疾患、虚血性腎疾患、多発性硬化症、外傷性脳損傷、脊髄の損傷、移植片対宿主疾患(GVHD)、糖尿病、慢性閉塞性肺疾患(COPD)、関節リウマチ、固形臓器移植による傷害、整形外科の傷害、軟骨障害、創傷、またはそれらのあらゆる組合せである、前述の実施形態のいずれか一つに記載の方法。
実施形態20.1つまたは複数の追加の再生療法を投与することをさらに含む、前述の実施形態のいずれか一つに記載の方法。
実施形態21.1つまたは複数の再生療法が、骨髄に由来する間葉系幹細胞、脂肪組織、胎盤組織、臍帯、ホウォートンゼリー、月経血、幹細胞、M2マクロファージ、単球、またはそれらのあらゆる組合せである、実施形態20に記載の方法。
実施形態22.幹細胞が、神経前駆細胞、内皮前駆細胞、臓器特異的な内因性幹細胞、またはそれらのあらゆる組合せである、実施形態21に記載の方法。
実施形態23.臓器特異的な内因性幹細胞が、心臓のckit+細胞である、実施形態22に記載の方法。
Claims (23)
- 患者の臓器または組織における虚血または炎症状態を処置する方法であって、該臓器または組織におけるCAMKK1のレベルの増加を誘導することを含む、方法。
- 前記臓器または組織が、心臓、肝臓、腎臓、脳、脊椎、肺、小腸、大腸、動脈、関節、軟骨、皮膚、またはそれらのあらゆる組合せである、請求項1に記載の方法。
- 前記臓器または組織が、前記心臓または心筋である、請求項2に記載の方法。
- 前記臓器または組織におけるCAMKK1のレベルの増加が、CAMKK1タンパク質を前記臓器または組織に投与することによって達成される、請求項1に記載の方法。
- 前記臓器または組織におけるCAMKK1のレベルの増加が、CAMKK1をコードする核酸を含むベクターを前記臓器または組織に投与することによって達成される、請求項1に記載の方法。
- 前記ベクターが、プラスミドまたはウイルスベクターである、請求項5に記載の方法。
- 前記臓器または組織におけるCAMKK1のレベルの増加が、増加したレベルのCAMKK1を生産するように改変された細胞を投与することによって達成される、請求項1に記載の方法。
- 前記臓器または組織におけるCAMKK1のレベルの増加が、前記CAMKK1のレベルの増加がもたらされるように改変された細胞の培養物からの馴化培地を投与することによって達成される、請求項1に記載の方法。
- 前記細胞が、CAMKK1をコードする核酸を含むベクターで改変された、請求項7または8に記載の方法。
- 前記ベクターが、プラスミドまたはウイルスベクターを含む、請求項9に記載の方法。
- 前記細胞が、CAMKK1の発現を誘導する薬剤で改変された、請求項7または8に記載の方法。
- 前記薬剤が、TGF−β、miR145、Dab2阻害剤、またはそれらのあらゆる組合せである、請求項11に記載の方法。
- 前記Dab2阻害剤が、Dab2のsiRNAである、請求項12に記載の方法。
- 前記CAMKK1が、構成的に活性なCAMKK1である、請求項1に記載の方法。
- 前記構成的に活性なCAMKK1が、CAMKK1 1−413トランケート型を含む、請求項14に記載の方法。
- 前記構成的に活性なCAMKK1が、T108A突然変異CAMKK1、S459A突然変異CAMKK1、またはT108A/S459A突然変異CAMKK1を含む、請求項14に記載の方法。
- 前記タンパク質、ベクター、細胞、または馴化培地が、全身投与されるか、虚血もしくは炎症を起こした組織に直接投与されるか、または虚血もしくは炎症を起こした組織の周辺に投与される、請求項4、5、7、または8のいずれか一項に記載の方法。
- 前記細胞が、間葉系幹細胞である、請求項7または8に記載の方法。
- 前記虚血または炎症状態が、急性心筋梗塞、心不全、末梢動脈疾患、卒中、肝疾患、虚血性腎疾患、多発性硬化症、外傷性脳損傷、脊髄の損傷、移植片対宿主疾患(GVHD)、糖尿病、慢性閉塞性肺疾患(COPD)、関節リウマチ、固形臓器移植による傷害、整形外科の傷害、軟骨障害、創傷、またはそれらのあらゆる組合せである、請求項1に記載の方法。
- 1つまたは複数の追加の再生療法を投与することをさらに含む、請求項1に記載の方法。
- 前記1つまたは複数の再生療法が、骨髄に由来する間葉系幹細胞、脂肪組織、胎盤組織、臍帯、ホウォートンゼリー、月経血、幹細胞、M2マクロファージ、単球、またはそれらのあらゆる組合せである、請求項20に記載の方法。
- 前記幹細胞が、神経前駆細胞、内皮前駆細胞、臓器特異的な内因性幹細胞、またはそれらのあらゆる組合せである、請求項21に記載の方法。
- 前記臓器特異的な内因性幹細胞が、心臓のckit+細胞である、請求項22に記載の方法。
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EP2687219A1 (en) * | 2012-07-18 | 2014-01-22 | Universität Duisburg-Essen | Use of preparations comprising exosomes derived from mesenchymal stem cells (MSCs) in the prevention and therapy of inflammatory conditions |
US20160206550A1 (en) * | 2013-08-29 | 2016-07-21 | Stempeutics Research Pvt. Ltd. | Stromal dells derived conditioned medium, method of obtaining said conditioned medium compositions, formulations and applications thereof |
AU2015355188B2 (en) | 2014-12-01 | 2021-08-26 | Northeast Ohio Medical University | CAMKK1 as a novel regenerative therapeutic |
CN107249604A (zh) | 2014-12-31 | 2017-10-13 | 人类起源公司 | 使用自然杀伤细胞治疗血液病症、实体瘤或感染性疾病的方法 |
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JP2021098717A (ja) * | 2014-12-01 | 2021-07-01 | スンマ ヘルスSumma Health | 新規の再生治療剤としてのcamkk1 |
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CA3007055A1 (en) | 2016-06-09 |
JP2021098717A (ja) | 2021-07-01 |
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RU2017122817A (ru) | 2019-01-10 |
JP6893873B2 (ja) | 2021-06-23 |
AU2015355188A1 (en) | 2017-07-20 |
BR112017011490A2 (pt) | 2018-02-27 |
KR20170088988A (ko) | 2017-08-02 |
US20220233653A1 (en) | 2022-07-28 |
KR102610068B1 (ko) | 2023-12-06 |
IL252612A0 (en) | 2017-07-31 |
US11273208B2 (en) | 2022-03-15 |
IL284408B (en) | 2022-06-01 |
IL252612B (en) | 2021-07-29 |
EP3940068A1 (en) | 2022-01-19 |
EP3227441A1 (en) | 2017-10-11 |
KR102460983B1 (ko) | 2022-10-31 |
KR102236843B1 (ko) | 2021-04-07 |
WO2016089826A1 (en) | 2016-06-09 |
CA3007055C (en) | 2023-08-01 |
CL2017001390A1 (es) | 2018-05-11 |
KR20220151004A (ko) | 2022-11-11 |
UA124450C2 (uk) | 2021-09-22 |
EP3227441B1 (en) | 2021-06-30 |
IL284408A (en) | 2021-07-29 |
KR20210010662A (ko) | 2021-01-27 |
AU2015355188B2 (en) | 2021-08-26 |
RU2017122817A3 (ja) | 2019-06-11 |
EP3227441A4 (en) | 2018-08-15 |
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