20240722_183324

meeting	https://mytakeda.sharepoint.com/:f:/r/teams/TCAL/Departments/CNS/PROJECTS/NLRP3%20Inflammasome/Core%20Team%20Meetings/2024?csf=1&web=1&e=O4bnhN
Bi-weekly Biomarkers' Meeting	📁 2023
Joint meeting	https://mytakeda.sharepoint.com/sites/InterACT-RAD-Pipeline/NLRP3%20Inhibitor/Shared%20Documents/Forms/AllItems.aspx?RootFolder=%2Fsites%2FInterACT%2DRAD%2DPipeline%2FNLRP3%20Inhibitor%2FShared%20Documents%2F01%5FMeeting&TID=0x012000793CD60BC65C13458F56FF0F6488CB5E&View=%7B9232E2CD%2DDFB8B%2D46BC%2DDA4EE%2D055039848432%7D
timeline	📊 NLRP3 Timeline toward CS_202308.pptx 📊 Timeline_NLRP3_CN_Candidates.xlsx
all studies and required amounts for CN compounds – edit the studies and fill the deadline	📊 NLRP3_CNCS candidate_assay list.xlsx
postmortem	📁 Translational biomarker data

Sleep

{Zielinski, 2017 #2354}

	{Zielinski, 2017 #2354}
PD		sleep deprivation LPS	↑ NLRP3 inflamasome	↑ IL-1b ↑ wakefulness	↑ NREM sleep delta power ↑ sleep
					↓ NREM sleep ↓ sleep amount and intensity (delta activity) following SD
Tx			NLRP3 KO	↓ IL-1b	↓ NREM d power (Takahashi, 1997 #2384, 원문 X)
			IL-1RF

TAU

202204 Nlrp3 meeting with tau	aSyn : c term cleavage sz: cd68 other inflammation athway: → 70% tspo is non specific to nlrp3 tau oligover-replication (Meisl 2021) than spread oligomer assay?
	pd stratification: elena we don't want stratification causality SZ: Symptomtic vs prophylactic Simen: NLRP3 activates caspase-1
NLRP3 Boston, Jul 18	- Overall Small magnitude of effect. - aSyn fragment animal model: 우선 WB로 해라, (& rat CSF?). SZ: LCMS's pos is 10%, Atuka won't be able to do it. - assay adequately resourced - AD Aβ is off-strategy, p-tau would be good evidence SZ: Longi is redundance, [MP] PD Nice to have but NOT must have: NLRP3 PET tracer A-SYN PET tracer to be further pursued for multiple programs (to be better resourced and explore all avenues in parallel) - Paul/Ashley to take action MUST have a pathway biomarker – can serve as TE biomarker too Explore measurement of ASC-Specs in blood MUST have disease biomarker: show drug effect on the levels of a-SYN Nice to show drug effect (inhibition) on caspase-1 truncation of a-SYN Nice to be able to measure fragments of a-SYN in vivo animal models (brain homogenates and/or CSF) Nice to have developed the assay for measuring a-SYN fragments in human CSF by CS (March 2023) Agreement with Arthur regarding the criteria for clinical biomarkers will be set back in December – more discussions to follow AD Steve to share with everyone the cytokine data on AD subjects Arthur concerned about the magnitude of the effect in clinical trials Show drug effect on p-tau

TCP

[TCP_NLRP3_20211111.pptx]

Timeline

[NLRP3 Timeline toward PE_20211119.pptx]

TMQB

• uploaded in 📁 [TMQB (2021Sep16,17)]

QB: 4th of November

• get validation and pharmacology: MP

modelling: MV

• Tracer: HS
• markers & Patient stratification: JL
• ety

B1: 11th of November

• cember

16th of December

er	Section	Topics	Template (in the attached '202106 TMQB Slides Revised. Pptx')	Presenter at TMQB	Presentation time (min) at TMQB
	Executive Summary			Jaewon	2
	Target validation	•Human genetic/post-mortem data • Animal models of disease mechs	P7	Marianthi	15
	status of asset generation			Huikai	5
	Safety	•TSR • safety biomarkers, and necessary de-risking	P8	Heather Estrella	10
	Quantitative Pharmacology Targets	•PK-PD relationships •prediction of human response	P9	Michael Vilkhovoy	10
	Clinical BMx Feasibility	BMx Options and Usage Map	P10, 11	Jaewon	13
	Translational Probability of Success (TPoS)	Scoring Framework	P12	Jaewon	5
Total					60

Transfer

		https://teams.microsoft.com/_#/files/General?threadId=19%3Ad1040cfe9f3149368562d0a6d0cbf91a%40thread.tacv2&ctx=channel&contfolder=%252Fsites%252FMBMTSHO%252FShared%2520Documents%252F02_MBM%252FPrograms%252FNLRP3
After Oct 29
n	Harvda
oo	Harvda	NLRP3 assay: MSD ELISA

Team

[NLRP3 FTE&Budget_20211119.xlsx]

English

In vitro, NLRP3 radioligand,

Uncertain Spans

location	transcription	uncertainty
Sleep section	leftmost cell labels above the {Zielinski, 2017 #2354} row	The header row is mostly blank in the photo; only the citation cell is legible.
TMQB list	”QB: 4th of November / B1: 11th of November / cember / 16th of December”	The leading characters are partially cropped; reading order preserved.
TAU NLRP3 Boston Jul 18 box	bullet character before each cyan-highlighted line	The dash/bullet markers vary; preserved as - per cell visual.
Transfer leftmost cells “n / oo”	row identifiers for Harvda rows	The leftmost glyphs are partially cut off; preserved as-seen.