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- 2018/02/14
- 非アルコール性脂肪肝炎(NASH)モデルマウス、アトピー性皮膚炎モデルマウス(IL33 Tgマウス)を追加しました。
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- 2017/09/13
- 遺伝子改変マウスを用いた非臨床試験受託ページを開設しました。
QPS社の神経変性疾患に関する非臨床試験受託
高齢化社会を迎え、パーキンソン病、アルツハイマー症などの中枢神経系に障害を生じる神経変性疾患の患者数はますます増大する傾向にあり、これらの神経変性疾患に対する治療薬研究・開発が激化しています。トランスジェニック社では日本における神経変性疾患の研究・開発をサポートするために、世界的に評価の高いオーストリアのQPS社 (QPS Austria GmbH) のサービスをご提供しています。
QPS社では様々な神経変性疾患の創薬において、in vitro, in vivoの非臨床試験から、臨床試験までの受託・コンサルタントサービスを行っております。特に非臨床薬理試験においては、病態モデルとなる遺伝子改変動物を用いたユニークな薬物評価系を保有しています。表はその評価系の一部を示したものです。
in vivo 評価系
| Indication | Strain Name | Species | Mutation | |
|---|---|---|---|---|
| Construct | Promoter | |||
| AD human APP/Aβ |
APPSL tg | Mouse | human APP751SL-h London (717) & Swedish (670/671) mutation | murine Thy-1 |
| Tg2576 | human APP695 with double mutations at KM670/671NL | hamster prion protein gene | ||
| 5xFAD | human APPSwFlLon, PSEN1 * M146L * L286V 6799Vas/J | murine Thy-1 | ||
| TBA2.1 | truncated mutated human Aβ(Q3-42) | murine Thy-1 | ||
| TBA83 | N-truncated human Aβ(4-42) | murine Thy-1 | ||
| APP homo | Rat | human APP751 with Swedish and Indiana mutation | murine Thy-1 | |
| AD human TAU |
TMHT10 hTau (V337M, R406W) | Mouse | human TAU441 bearing the missense mutations V337M and R406W | murine Thy-1 |
| TAU (P301L) | human TAU with the P301L mutation | murine prion | ||
| genomic Tau | 6 human Tau isoforms, no endogenous Tau | human Tau | ||
| TAU (P301L) | Rat | human TAU40 with P301L mutation | murine prion | |
| AD crossbreds |
APPSL x ApoB100 | Mouse | human APP751SL-h London (717) & Swedish (670/671) mutation & human ApoB100 | m Thy-1, h ApoB100 |
| APPSL x hQC | human APP751SL-h London (717) & Swedish (670/671) mutations & hQC | murine Thy-1 | ||
| 5xFAD x hQC | human APPSwFlLon, PSEN1 * M146L * L286V 6799Vas/J & hQC | murine Thy-1 | ||
| PD | D-Line | Mouse | wildtype human α-synuclein | human PDGF-β |
| Line-61 | wildtype human α-synuclein | murine Thy-1 | ||
| A53T | human α-synuclein with mutation A53T | human PDGF-β | ||
| HD | R6/2 | Mouse | human Huntington with 110-125 CAG repeat expansions | - |
| BAC HD | Rat | human Huntington with CAG repeat expansions | Rat HD | |
| ALS | (SOD1-G93A)1Gur/J | Mouse | human SOD1 with G93A mutations | murine Thy-1 |
| ALS-FTLD | TDP43 | Mouse | human wildtype Tar DNA Binding Protein-43 | murine Thy-1 |
| Hyperlipidemia/ AD | ApoB100 | Mouse | human ApoB-100 | human ApoB100 |
| Niemann-Pick disease type C1 | NPC1-/- | Mouse | knockout | - |
in vitro 評価系
| Indication | Cell system | Assay | Read out |
|---|---|---|---|
| Parkinson’s Disease | Primary TH neurons | Survival and Apoptosis determined by Image based analysis using TH, MAP2 and Annexin V (or cleavedcaspase 3) | % TH neurons of total or MAP2 positive neurons % apoptotic cells of TH % apoptotic cells of MAP2 |
| Primary TH neurons | Image based analysis using synapsin, MAP2 and TH | Synapses in TH positive and MAP2 positive neurons | |
| Primary TH neurons | Image based analysis using TH and tubulin | Dendritic networkof TH neurons outgrowth determined as immunoreactive area) | |
| Primary TH neurons | PD relevant lesions (e.g. MPP+, 6-OHDA) in combination with image based analysis | % Survival of TH and MAP2 neurons % Apoptosis of TH and MAP2 neurons Synapses in TH and MAP2 positive neurons Effects on mitochondrial activity or distribution | |
| Hippocampal neurons | BrdU Incorporation (Image basedanalysis) | Neurogenesis | |
| SH-SY5Y and RN cells overexpressing wildtype α-synuclein or A53T | Compound effects on synuclein levels (ELISA) alpha synucleinaggregate induction(image based analysis) Synucleinand autophagy Synucleinand synapses (image based analysis) Mitochondrial profile (image based analysis) | Synucleinlevels Synucleinaggregate induction (image based analysis) Synapses in synucleinoverexpressing cells Mitochondrial profile (activity and distribution) | |
| Primary cortexand hippocampal neurons | PD relevant lesions (MMP+, 6-OHDA, BSO) and 96-well-plate readout | Survival (MTT), Toxicity(LDH), Apoptosis (caspase 3, YOPRO) or mitochondrial activity (mitotracker) | |
| Primary human fibroblasts from PD patients | MMP+ / 6-OHDA | Survival (MTT), Toxicity(LDH), Apoptosis (caspase 3, YOPRO) or mitochondrial activity (mitotracker) | |
| SH-SY5Y or PC12 | Colorimetric assay | Acetylcholinesterase activity | |
| Microglial cell lines (Bv-2, C6, HMO6) | Inflammation | Cytokines, oxidative stress | |
| Amyotrophic Lateral Sclerosis | Motor neurons | Glutamate lesion | Viability (MTT), Toxicity (LDH), Apoptosis (caspase 3, YOPRO), Mitochondrial profile (activity, membrane potential, shape) |
| Primary neurons | Glutamate lesion | Viability (MTT), Toxicity (LDH), Apoptosis (caspase 3, YOPRO), Mitochondrial profile (activity, membrane potential, shape) | |
| SH-SY5Y cells overexpressing TDP43 | MTT or LDH YOPRO or caspase 3 Nuclear/Cytoplasmfractionation | Viability Apoptosis Translocation of TDP43 | |
| Huntington’s Disease | Primary neurons | Glutamate lesion | Viability (MTT), Toxicity (LDH), Apoptosis (caspase 3, YOPRO), Mitochondrial profile (activity, membrane potential, shape) |
| Stroke | Primary neurons | Glutamate or NMDA lesion | Survival (MTT), Toxicity(LDH), Apoptosis (caspase 3, YOPRO), Mitochondrial profile (activity, membrane potential, shape) |
| Alzheimer’s Disease | SH-SY5Y Hippocampal neurons Chicken neurons | Aβ toxicity assay | Survival (MTT), Toxicity(LDH), Apoptosis (caspase 3, YOPRO) |
| SH-SY5Y-hTau441 | Immunosorbent assay | Total Tau and phospho Tau sites (Ser202, 231, 262, 396, 181) | |
| Hippocampal neurons | Aβ oligomers and Image based analysis using Tau and actin | Missorting of Tau (soma & dendrites versus axon) | |
| Hippocampal neurons | Aβ oligomers and Image based analysis using tubulin | Scatteredneurites Neurite outgrowth | |
| Hippocampal neurons | Aβ oligomers and Image based analysis using synapsin and MAP2 | Synapses in Aβ positive MAP2 | |
| Hippocampal neurons | BrdU Incorporation (Image based analysis) | Neurogenesis | |
| Hippocampal neurons orcell line (exceptsynapses) | MTT or LDH assay YOPRO, caspase 3 activation Synapsin, MAP2 (image based) Tubulin (image based) Mitotracker(image based or fluorometric read out) | Viability Apoptosis Synapses Neurite outgrowth (tubulin) Mitochondrial activity | |
| Cells overexpressing APP Primary neurons | APP processing, gamma-secretase inhibitor | APP, Aβ peptides | |
| Microglial cell lines (Bv-2, C6, HMO6) | Inflammation | Cytokines, oxidative stress | |
| Microglial cell lines (Bv-2, C6, HMO6) | Amyloid clearance assay | Determinationof amyloid oligomers (modified A4 assay) inside | |
| SH-SY5Y-hTau441 | Screening for kinase inhibitors (Immunosorbentassay) | Total Tau and phospho Tau sites (202, 231, 262, 396, 181) | |
| SH-SY5Y-hTau441, SH-SY5Y | Hypothermia | Total Tau and phospho Tau sites (202, 231, 262, 396, Tau181) | |
| No cells | Tau aggregation and dis-aggregation assay | Fluorescent based detection Transmission Electron Microscopy | |
| No cells | Inhibition of Amyloidoligomer formation | Determinationof amyloid oligomers (modified A4 assay) | |
| SH-SY5Y or PC12 cells, or primary neurons | Acetylcholinesterase activity |
価格
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QPS Austria GmbH概要
ＱＰＳ社の神経薬理学部門は、神経変性疾患に特化したCRO、JSW Life Sciences社としてオーストリアのグラーツに1999年に設立され、その後QPS社に統合されました。パーキンソン病、アルツハイマー症など神経変性疾患の分野において、その科学レベル、技術レベルは高く評価され、世界の大手製薬企業から多くの試験の受託実績があります。トランスジェニック社はQPS社の非臨床試験に関する日本代理店となっております。
http://qpsneuro.com/
