JS PD KB

20240722_183351

7 min read

  • mito is limited to SN because oxidative stress of dopamine metabolism
  • Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates ROS) and DA oxidation can lead to endogenous neurotoxins, whereas some DA derivatives show antioxidative effects.2
  • lysosome: general problem (eg. Cortex), GBA goes to cortex
  • PD PRS subtyping: everyone is mixture of lysome mitochondira, continuous distribution, not cleanly separated
  • PRS-based microglia generation from fibroblast (DRI?)
  • Daria
    • Plan
      • Transcriptomics (subtype?)
      • eQTL
      • metabolomics to be available IN the future for AMP-PD

FOX-1: Marios politis:

total n=45, An observational cross-sectional study: to assess clinical, imaging and biologic markers, (PINK1, DJ-1, Parkin, SNCA).

i) presymptomatic stage of carriers of genetic PD mutations vs ii) symptomatic carriers of genetic PD mutations, iii)Spd AND iv) hv. Readouts: PET and SPECT (DA:[123I]FP-CIT SPECT and HT:[11C]DASB ), MRI (structure & function) blood, CSF (power calculation) A total of 10 subjects per genetic mutation cohort (five asymptomatic and 5 symptomatic per group) 근데 eight SNCA carrier랬는데.

  • Blood sample collection (up to 45 ml):
    • The total amount of blood needed for the routine clinical lab tests will be no more than 10 ml.
    • Whole blood for plasma (about 10ml) and serum (about 10ml) will be collected for analyte studies.
    • Whole blood will be obtained for the extraction of DNA sequencing/genomic analysis (about 6ml).
  • CSF (optional): 15-20 ml of CSF will be collected from study subjects
Total α-synOligomeric α-synTotal tau
Phosphorylated tauAβ40Aβ42

K-BIOX

Translation definitionLine drawing, starting from human
examplesFibroblasts, CMT, Klein STUDY
Hypothesis → test

KOLs

NameFieldProfessionAffiliationContactQuestions / NotesDetail
Marios politis[email protected]Co-principal investigator for our MC1 PET study
Christine KleinNeurologistUniversity of Lübeck,[email protected]
  • Parkin-PD: No dementia, but gait freezing, impulse control, 한국 (?)엔 exon deletion 많다, late AAO
  • Genetic burden: Park gene + GWAS gene
  • Reference studies: CAMPD, Real PET, (RASAGILINE'S delayed start)
  • Prodromal single heteroz's
  • Family history+ DATScan+ (no RBD) + updrs 4 (?)점, kinetic tremor제외?
  • -Mito 본질: ATP failure는 아니다 (demonstrated by Greenamyre, ATP 줄여도 No cell death), QC의 문제이다 {Tatsuta, 2008 #1481}
[future plan]
  • single hetero에서의 conversion
  • Vollstedt's poster보면 homo Parkin 401 vs hetero Parkin 177 인데?
  • mito PD
  • CONNECTION with Christine Klein?
김윤중용인세브란스010 6799 1666
[email protected]		20210512 call:
이지영보라매병원[email protected](iRBD, brain glucose metabolism pattern, phenoconversion, clinical predictor
유철형PDNeurologist강남세브란스[email protected]Connection with PPMI?Parkin, MSA, glucose metabolism, dyskinesia, GBA, PDD
Aya NaritaGDNeurologist (podiatry)Department of Orthoptics and Visual Science, School of Allied Health Sciences, Kitasato University, Kanagawa, Japan[email protected]
Hitoshi Ishikawa안과Kitasato University, Kanagawa, Japan
Satoshi Ishikawa안과
이필휴연세대 신경과[email protected]
유한욱 Han-Wook YooAMC[email protected]
Beom Hee Lee 이범희AMC[email protected]한국takeda와의 관계를 이유로 거절함. Department of Pediatrics
Medical Genetics Center
Asan Medical Center Children's Hospital
University of Ulsan College of Medicine
88 Olympic-Ro 43-Gil Songpa-Gu Seoul 05535, Korea
Fabry, galactosis etc, but not specifically GD
Focus on endocrinology
서울대 고정민희귀질환 울산경남권역센터장, GD!, one case report on GD, (ELIGLUSTAT VS ert), , media interview on GD,
서울대 김한준PD, MSA[email protected]Qs:
  • CamPAIN
서울대 전범석[email protected]
아주대 손영배
부산대 전종근Pusan National UniversityTel: +82-55-360-3158
Fax: +82-55-360-2181
E-mail: [email protected], [email protected]		Chong Kun Cheon, MD, PhD Division of Pediatric Endocrinology
and Metabolism, Department of
Pediatrics, Pusan National University
Children's Hospital, Pusan National
University School of Medicine, 20
Geumo-ro, Mulgeum-eup, Yangsan
50612, Korea
Horacio KaufmannNYU Langone[email protected]Interest: PD, MSA, autonomic disorder, clinical trial, Retinal abnormalities Dear Dr. Kaufmann:

Thank you very much for making time to meet with Takeda team regarding clinical trial design in MSA for our anti-asyn monoclonal antibody program.

Preliminary agenda items will include the following:
  • NfL and putaminal vMRI as a POC endpoints
  • Sensitivity of UMSARS to disease progression; possibility of extracting items or factors within UMSARS that are more sensitive to disease progression
  • Sensitivity of UMSARS
  • Suggestions on sources of natural history data for clinical trial design and sample size estimation
With much appreciation,

Jaya Padmanabhan, MD
Kyoto National Hospital, KyotoHideyuki Sawada should be the leader.pdd보유, {Oeda, 2015 #880}
Juntendo university, TokyoNobutaka Hattori should be the leader.
https://www.juntendo.ac.jp/english/research/hattori_nobutaka.htm		Taku Hatano, Shin-ichiro Kubo (my predecessor, associate professor)
Ehime universityMasahiro Nomoto,a,* Masahiro Nagai (next generation, to go person)
https://www.researchgate.net/profile/Masahiro_Nomoto		 They have Phase I centre (Yan, (Yan, Nonomura Hidenori from TDC-Japan 주전)
  • Discussion topics
  • NLRP3: inflammation in sPD, NLRP3들 characterize (ie chatterjee들 반복)→ cut off 설정, 실험근거 생성과 병행, Severity와 correlatio되는 CSF증거는 아직 없나. Correlation (calibration) between NLRP3 (etc) & Datsan, : cross-sectional, baseline NLRP is prognostic of rapid datscan/clinical progression?, & UPDRS score, plasma, NDE, aSyns
  • PK-PD-Efficacy?
  • GBA: cognition, vMRI in PDD, DLB, PD-MCI
  • 그늘의 경험
  • # CSF feasible? Postmortem brain 도 했나네.
# mice study 했나네 # UPDRS 경험. # pk, pd # DaTscan # urate trial #animal model (MPTP)
  • Introduction of Takeda's PD discovery pipeline
  • The needs of Natural history data to identify/characterize biomarkers :
    • eg. inflammatory biomarkers and mitochondrial biomarkers to correlate with disease progression
    • or for patient selection in PD
→meeting summary:
  • Inflammation: ↓aSyn → ↓ inflammation? NLRP3 may be confounded by age, NSAID, GLP-1 -->
  • mitochondria: Mitochondrial encephalomyopathy(MELAS), GDF15, recommended Dr. Hattori for mito
[Planning-20210212 call with Nonomura]
  • In person or virtual
  • General topic → slides (q&a maybe?)
  • CDA, Fee (from NSTM budget)
  • Mar 8-12
  • Sample available? TBD, DATSCAN? TBD
  • YAN JOIN ? TBD, TAKEDA-SAN May join
  • They know TAK341, TAK071
  • NLRP3
Kitano Hospital,
The Tazuke Kofukai Medical Research Institute, Osaka, Japan,
Tatyana SimuniMD, FAAN Arthur C. Nielsen Professor of Neurology Division Head, Parkinson's disease and Movement Disorders Center NorthwesternUniversity Feinberg School of Medicine Abbott Hall 11th Floor 710 North Lake Shore Drive Chicago IL 60611[email protected]
Phone 312-503-2970 Fax 312-908-5073
RytenCrick institute & UCL[email protected] (?),{Billingsley, 2019 #1190},Publications: https://www.crick.ac.uk/research/find-a-researcher/minee-choi
Choi (최민이)조교수, 뇌인지과학과, KAIST웹사이트 mineechoilab.kaist.ac.kr[email protected]  [email protected]
https://www.linkedin.com/in/minee-liane-choi-99149ba4/?originalSubdomain=uk,
Telephone 042-350-6516		{D'Sa, 2023 #2426}: https://doi.org/10.1038/s42256-023-00702-9Prediction of mechanistic subtypes of Parkinson's using patient-derived stem cell models mechanistic

Uncertain Spans

locationtranscriptionuncertainty
Beom Hee Lee row inline tiny-font blockURL line and full Tel/Fax/E-mail of Asan Medical CenterThe Asan Medical Center contact block is rendered as a screenshot of a webpage with very small font; only address fragments are confidently legible.
고정민 row inline screenshotKorean web-UI labelsA small Korean webpage screenshot with bar/scale UI elements appears in the cell; preserved as evidence and not transcribed in the body.
Daria bullet “(DRI?)""DRI?” tagTrailing parenthetical near “PRS-based microglia generation from fibroblast” is small and possibly truncated; transcribed as seen.
FOX-1 paragraph “iii)Spd""Spd” / “sPd”Lowercase/uppercase boundary on “sPd” hard to confirm; transcribed as seen.
Choi row trailing “mechanistic”dangling wordA trailing highlighted “mechanistic” word appears alone at the bottom edge after the title, possibly cut off; transcribed as-seen.

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