BIOMARKER tracker continued (Oxygen consumption + LC3 II), Stage / Date / Deliverables panel, BMx Platform / BPS / Feasibility / BFA / Technical / BTV / IVC / GPT / Tox / BFP stage matrix, BioOrchestra opener (B amyloid CD36 microglia, miR-485-3p, ELAV12 / Sckeckel 2016 #1591)

BIOMARKER tracker (continued)

row	content
Oxygen consumption	(rationale)
ATP / NAD+
NJF / NLRP3 / ACE	(assay status)
LC3 II	We (PMTGS program is intended this matter as a sham PD with PMTGS Inhibitor enhanced encryption and elevated CSF LC3 II in mock). The studies were aiming for therapy LC3 II A. Sebcal Medical Japanese (USc) will start identifying potential lead PD treatments / a few biomarker patient sample assessments. Will check the detectability of CSF LC3 II in the next a couple of months. 20240105 Steve / MJFF leagues SMG are screening antibodies. I think we have the flesh report in the coming week. Initially I want to test if CSF LC3 II is detectable or not within May. PV.

Stage / Date / Deliverables (small panel)

Stage	Date	Deliverables
Sample arrival	11.50	Sample arrival data 11.50
IP validation	11.40	IP confirmed by Western blot data is final
Phenotype	12.50	Sample shipped to academia for Sci or PreproSci confirmed in MS data

Wide tracker matrix

Stage	Molecular BMx	Neurocircuitry BM (1.51) (in vivo Tx response?)	Novel PET ligand	Existing Clinical or preclinical work is not done before BMG method (MRI or PET)
Milestone
BM Platform Start	In silico assessment of assay feasibility, reagents, standards, assay format	White paper on available datasets or techniques, vendors, analysis plan	PET Tracer proposal presented to PET steering Committee (Makoto, USE 가 가 진수 CSI)	Rationale & proposal for development
BPS	Go/NoGo @ TDIB based on Research plan with selected vendor	Go/NoGo @ TDIB based on vendor SOW or internal PE plan	Go/NoGo @ PET SC based on feasibility, cost, need	Go/NoGo from QTS-DDU-TAU based on feasibility, cost, need
Feasibility Assessment	Procure & verify compatibility of reagents and assay format; verify assay sensitivity in samples	Optimization of assay or contracting with vendors	BMax assessment	Survey of available internal options and/or partnerships
BFA	Prototype assay 개발이 일감 in clinical	Prototype assay	GNG at PET SC based on Bmax assessment	Vendor or internal SOW
Technical Validation	Achieve all assay acceptance criteria in vitro, e.g. dilutional linearity, etc	Pilot study of test-retest variability, etc	Optimization of physical properties and non-imaging triaging of potential candidates	Vendor/collaborator/Assessments (incl) [공유 가 7]
BTV	Spec sheet with assay wet lab quantified parameters	Technical validation in specific protocol procedures in place	Potential PET tracer candidates identified	Validate in Takeda (mc1, ex 가 가, 데 가, 호카, ex IMG-G candidate IMG (가만))
In Vivo Calibration (IVC)	In vivo BMx data package incl: PK/PD analysis in collaboration with DMPK	In vivo Preclinical biological of BcM longitudinal change & variability	Preclinical Test of PET studies in relevant preclinical species (e.g. NHP) → specific binding, dosimetry	Technical characteristics of marker in relevant population - face validity (1.50 MC.1.51 (in vivo))
GPT in TX 1 BCS	Approved by MBM SC as ready for use in preclinical POC(1) [개사가가] or EM study	Approved by NCB SC as ready for use in preclinical POC or EM study	Approved by PET SC as fit-for-purpose for preclinical use, it is understanding that a detailed clinical PET study is not formalized until a GPT is formed	QTS-IMG as ready for preclinical use - construct validity
Tox	Human use qualification	Human matrix assessment / patient samples	Preclinical testing of BMx longitudinal change and variability	GLP Tox IND-enabling studies (가공/가가 가/가 다/가 다); FIH T/RT and dosimetry; Assessment in relevant population for drug development use case = construct validity (가) MC1 (양감지수 가 다)
BFP	Approved by MBM SC as ready for clinical use in TAK study	Approved by TDIB as ready for clinical use in TAK study	Approved by PET SC as ready for clinical use in TAK study	Approved by QTS-IMG as ready for clinical use in TAK study
BM Types	TE << PD, DR >> PS	PD, DR >> PS	TE << PD, DR >> PS	PD, DR >> PS

BioOrchestra (start)

B amyloid activates microglia through CD36 (a receptor) → microglia release cytokines

	content
1 miR-485-3p expression (check 5, 2) (in which cell type?)	Data: IP p32 / 1 in hippocampus in 5x FAD mice (but not in cortex), miR is increase in CK D/A vs WT how about in AD patient? (T-1)
2 ELAV12 (ELAV-like RNA binding protein 2)	Evidence How much decrease in AD patient? (T-1); Data: IP p35 / 1 (half) in hippocampus in 5x FAD mice (but not in cortex) half (소뇌 외 5x WT)
(Sckeckel 2016 #1591)	The binding of ELAV-like proteins onto Y-RNAs were observed in neurons grown in the laboratory that had been briefly stressed by exposure to ultraviolet radiation (interrupted in normal RNA targets)
	some messenger RNAs targeted by neuronal ELAV-like proteins showed altered regulation after stress
	Such changes to the normal messenger RNAs could have a large impact on the proteins that are produced from them

Aliquot CD36 / ↓ PGC-1alpha in AD