| correlation), variability는 다른 얻을수도 o, calculation for AAV rat study, | assay power | |||||
| non-CAD non-phenol Series 5c |
Discussion on de-prioritizing of TR847: → to make a decision of go/nogo for TR847 by end of September
| TH WB - TH IHC - DAT ARG - DATscan - VMAT2 PET TSPO WB - TSPO PET | ||||
| Series 3 non-CAD | ||||||
CNS BM, Pathogenic, priority, AAV aSyn rat, → CSF (Oct), ,
| TSPO WB | TSPO IHC | TSPO ARG [3H]PBR-28 | TSPO PET | |
|---|---|---|---|---|
| Rat AAV-asyn Tentative Study Design Readout | ip LPS rat | Cortex |
| VMAT2 WB | VMAT2 IHC | VMAT2 ARG | VMAT2 PET ([18F]AV-133) | |
|---|---|---|---|---|
| Rat AAV-asyn Tentative Study Design Readout (tentative) |
- Before PDE: TH WB (striatum) → DAT OD (striatum) - After PDE: {Molinet-Dronda, 2015 #2364} unilateral and bilateral 6OHDA RAT longitudinal in-vivo study, Striatum | |||
| (Sossi et al. 2022, PMID 35524682) aSyn PFF rat DAT OD vs DATscan |
AD
In vivo
| Animal model | Tau P301L (=rTg4510 일걸) at ReMynd |
| Tx | systemic LPS vs local BzATP |
| Read | Tau and inflammation |
NBB (project number: 1513)
| 02210 5 |
tissue advisory board (TAB) discussed and approved your application. reserved all of the available samples. on tab1 https://mytakeda-my.sharepoint.com/:x:/r/personal/jae-won_lee_takeda_com/Documents/NLRP3%20inhibitor/AD/NBB/sample%20selection/1513_Selection_01b.xlsx?d=w4962aba899c04fe58fe6937e5a1a2bfd&csf=1&web=1&e=JqaaQX 50 csf samples of AD donors (frozen samples) 21 plasma samples of AD donors (frozen samples) 17 hippocampal samples of AD donors (frozen samples) 42 hippocampal samples of AD donors (paraffin embedded) s.i.c.c? Dementia with Senile Involutive Cortical Changes (DEM-SICC), in which the pathology resembles AD, but does not qualify according to all neuropathological criteria. 38 csf samples of dementia donors (frozen samples) 22 plasma samples of dementia donors (frozen samples) 27 hippocampal samples of dementia donors (frozen samples) 35 hippocampal samples of dementia donors (paraffin embedded) 50 csf samples of control donors (frozen samples) 6 plasma samples of control donors (frozen samples) 6 hippocampal samples of control donors (frozen samples) 21 hippocampal samples of control donors (paraffin embedded) |
Assays of pyroptosis
| Human CSF | Human blood | PBMC | |||
|---|---|---|---|---|---|
| roglia | IBA-1 | ||||
| P3 | (Luo, 2019 #1852) control n=16, 33.9y, (0.92 ± 0.45 ng/ml) | (Chatterjee, 2020 #1263) IN pd, iMark Microplate Reader, BIORAD, USA. | (Fan, 2020 #657) | ||
| (Peng, 2019 #1853) control n=26, 38.8, 대략 <1 ng/ml) | Havrda MSD: detection range from 0.78 ng/mL (Sebastian call this LLOQ), 16.2+ ng/mL (%) — 90th percentile | ||||
| • None in PD | |||||
| ab253423, detection &capture antibody, both rraised against |
[Sebastian] ELISA: Cusabio ELISA (CSB E15885h) (The capture antibody is mouse monoclonal and the detection antibody is goat polyclonal.) Sensitivity (LLOQ) : 0.039 ng/mL Detection Range : 0.156 ng/mL-10 ng/mL CRO: RayBiotech | ||||
| N-term fragment? |
20220302: detected from 0.141 (ng/mL) js:거의 광고대로 됐네.어쨌건 Havrda's MSD보단 better 인 듯., NLRP3 in CSF could not be detected. NLRP3 in plasma was detectable but the dilution linearity did not meet the criteria. MSD: Antibody pair from abcam ELISA kit was used to develop MSD NLRP3 assay. However, as S/B ratio even at 60 ng/mL was as low as 3.3 [SMCxPro]: antibody pair (ab253423, abcam, produced by immunization with N-term fragment), full-length recombinant NLRP3 protein (ab165022, abcam, epitope unknown), 20220428: -buffer: LLOQ of 44 pg/mL(S/B ratio at 60 ng/mL was dramatically increased to 829, (250-fold higher value than that in MSD) -CSF: 0.17 ng/mL, couldn't get MRD because all diluted samples were below LLOD (ie no linearity, why?) -plasma: 4.45 ng/mL, MRD=2 - in both CSF & plasma: spke-recovery was low (~25%), Issues: low recovery (CSF & plasma), no MRD set up (CSF) where is the epitope in the full-length recombinant protein (for our standard and spike-in) and Abcam's NLRP3 ELISA's N-term fragment? Js: 다음 조건 충족이 중요할 것 -High S/B ratio in HC | ||||
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| Top header row “correlation), variability는…“ | partial leftover from previous-page table | Top row appears to be the tail of a planning-table column from the previous capture; reading order is preserved as-seen. |
| TSPO WB / IHC / ARG / PET cells | inline scatter plots and box plots | Plots are kept as evidence; numeric data points and group-label text inside each plot are below the legible threshold. |
| VMAT2 ARG plot panel C | ”p < 0.0001, R² = 0.8251” with axis labels DAT Intensity vs BPND | Axis tick labels (e.g. 6×10⁶) are partially blurred; numeric values preserved as best-effort. |
| Series 5c bullet list | ”If we drop TR847 we go for AAV model with TR980. Meanwhile model is established based on BzATP and TH and PK data.” | Tail of the line (“Meanwhile model is established”) may continue beyond the visible cell width. |