Imaging cost: $5,000/person, $500,000/100 persons, $300,000/60 HAB persons
[collaboration Research agreement: (not a contract)],
- payment schedule (something like 33% upfront, 33% in the middle and 33% at the end or any other breakdown they like - our policy indicates as much as possible should be milestone based
- a research plan included in the agreement as appendix and not a SOW.
- access to existing data
- If they are flexible, Takeda prefers to provide the first draft (also through cmdi)(Barrett, Cindi.Cindi.Barrett@Takeda.com).
Potential collaboration scope
Data access to subject-level, item-level data on all available subjects for clinical scale assessments and biomarkers (DICOM imaging data)
Sample access to available CSF and plasma for our analysis
Funding for longitudinal assessment (F/U 18F-DPA-714 imaging, $300,000 for 60 subjects)
Collaboration research objective
To characterize BMs profiles
To assess relationship of BMs i) between tissues, ii) with clinical outcome measure, iii) temporal change.
| Sponsor | Application timeline | Cohort | n / description | HC ? | Visit timing | O | 약화 ? | |
|---|---|---|---|---|---|---|---|---|
| MJFF | Application Aug → review Oct → decision Nov | NET PD FS-ZONE (NCT01280123) Pioglitazone | 217 individuals with early PD | X | BL, 16 weeks, and 44 weeks. | O | ? | |
| LCC | 200 PD and 230 controls of AJ descent. | Approvable only for LRRK2 study? | ? | ? | ||||
| PARS | 301 prodromai | |||||||
| PPMI | 423 PD, 196 hv | PPMI is a replication cohort so has a high bar. | 자격충분 | O | ||||
| SURE-PD 2 | 75 early PD | X | baseline, week 12 (CSF) and months 6 and 18 | O | ||||
| BioFind | Discover cohort | Cross-sectional | ||||||
| PPMI |
Dig in for (n=~100 longi) cytokines (?) - olink (CSF & plasma); olink CSF & plasma 데이터를 PD 와 plasma in the PD patients 에 관심이 있는데, 분석 가능하겠나?
| ||||||||||||||||||||||||||||||
| NGP |
Meeting 20220727 @Clotilde Degroot, Ms.:
Future: 60 longi plasma samples from PD in 12 m, and same number from HC (under NGP) MDS-UPDRS worsening 부터 확인필요치 않니? we have longitudinal MDS-UPDRS for 15 of them. CSF: - 13 samples from a single PD patient. - 300 CSF samples from 14 different "control" patients as ... Before submitting a proposal for access to C-BIG material and/or research study by a duly constituted Research Ethics Board (REB), the applicant must obtain approval for the research study by a duly constituted Research Ethics Board (TDC). Clinical Biospecimen Imaging and Genetic Repository (C-BIG) Application form 작성시 아래 활용하자: 8. DATA PROTECTION. Recipient acknowledges the importance of data privacy of individuals to whom accessed data and samples may relate and commits to comply with all applicable federal, provincial and local laws and regulations relating to data protection and the privacy of subject health information, not to attempt to identify subjects, and not to combine accessed or derived data with other sources of data that would lead to the identification of any individual [Reporting] It is the view of the MNI that this goal is achieved if research results remain publicly accessible without any restrictions. 3.3 Recipient will provide Provider with a written report on the progress of the Research Project described in Schedule 'A' within thirty days of the end of each Anniversary year of this Agreement; → They mentioned that they have always found a compromise with all groups for the type and timing of some return of the possible results. [publication] The Parties are committed to the principle of rapid release of research results to the scientific community and to disseminating all research results as widely as possible. ... In the event that no scientific publication arises from the Research Project, Recipient also agrees that written reports on the progress of the Research Project will be published in the C-BIG public dataset (?). | ||||||||||||||||||||||||||||||
| CN Otake 20220914 | CSF!! (only in IL18): 13 HC Logntidunal, zero PD ptietns has long, 9 PD has cross-sectional data. They have H&Y. |
Metabolomics
| {Olona, 2022 #2348} | Upstream metabolomics of NLRP3 |
Microglial Imaging
objective, define region for P1b, success criteria, timeline, budget, signal window, parameter, test-retest, check list, as a PD marker
| In vitro | In vivo preclinical: single (동물?) | In vivo preclinical 2 → 24 → 48 hr | Patient study | In vivo multiple dose |
|---|---|---|---|---|
|
[18F]DPA714 and [18F]FEPPA, tic NLRP3/TSPO relationship in postmortem human tissue and PD) (→ select between tracers) | 2 → 24 → 48 hr |
. AAV-αSyn mouse PKPD relationship will be assessed. However, transfer to TBOS will be evaluated by ATUKA Subchronic mouse models which are tested in TSD site one option. • Using ... be confirmed, e... after compound administration (Day0, 1 and X) | optimization of kinetics and protocol in a small number of HV/PD patients |
eg Amsterdam UMC to assess NLRP3/TSPO relationship |
| 21129: We are actually having both 18F compounds made (DPA-714 and FEPPA), at our collaborators at DFCI. The precursor and standard for both compounds are commercially available and all in vitro work will be done with both these compounds. Once we have an assessment of what tracer provides a larger specific window → we can conduct some preliminary in vivo PET imaging work to confirm the in vitro findings. | ||||
sort of preclinical validation we need to make the commitment to move to human
- E.g. Rat model of neuroinflammation (6-OHDA 인지 확정)
- To compare existing TSPO tracers ([18H]DPA714 and [18H]FEPPA)
Patient Imaging study
- To optimize kinetics and protocol in a small number of HV/PD patients
- we should expect from a potential clinical study with TSPO
Genotyping 방법 → lab
TSPO SNP genotyping using frozen brain tissues rs6971 polymorphism in the TSPO gene causes an amino acid substitution (Ala147Thr) within the transmembrane domain where the cholesterol-binding pocket is located. (C/C, C/T, T/T)
- DNA level: A>G, Sequence name Change
- GRCh38.p13 chr 22 NC_000022.11:g.43162920 A (reference allele)>G (alt allele), located in exon 4 of the TSPO gene
- Protein level: amino acid substitution (Ala147Thr),
- T (ACG) > A (GCG) Coding Sequence Variant, Missense Variant
- Frequency: A: 20-30%, G: 70-80%
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
MJFF cohort table / column boundaries | the longitudinal cohort table has 6 rows (NET PD FS-ZONE / LCC / PARS / PPMI / SURE-PD 2 / BioFind) and 7-8 visible columns including HC indicator and 약화 status; per-row column placement is partly inferred from cell width visible in body_r02_c01.jpg. | low confidence on column-by-row placement. |
NGP cohort accounting / RBD Blood column | the RBD / Blood* cell reads 32**; the **RBD: 15 have samples from MNI at the W and 14-month follow up, blood TBOS at Sacre-Coeur (Ron Postuma's site). footnote is partly clipped. | low confidence on the trailing footnote text. |
[Reporting] paragraph / Anniversary clause | reads within thirty days of the end of each Anniversary year of this Agreement; (red text); preserved verbatim. | low confidence on whether the clause includes additional sub-clauses clipped at the cell edge. |
Genotyping section / DNA level Sequence name Change | reads DNA level: A→G, Sequence name Change; the Change token is followed by a hyperlink that is not legible in the available crop. | low confidence on whether Change is a label or part of a hyperlink anchor. |