PET aSyn vendor matrix tail (Animal Cold/Hot, Animal in vivo PET, ARG, Preclinical Tox 2-rat studies, FH Protocol Eval, Protocol B-safety, FH F/U + team note, Four αSyn isomers, Alzforum half-life note)
PET aSyn vendor matrix (continued)
| AC Immune | MODAG | University of Zurich | QST | Shenzhen | Merck | Mass Gener at Brigham | |
|---|---|---|---|---|---|---|---|
| Animal section: Cold + Hot | FIG1 IF AAV α-asyn mice patient (MSA, DLB) FIG3 IF WT mice 5xFAD Tau P3015 AAV-α-asyn AS3T mice α-injected FOSO28 (2 quantification); AS3T mice Kd 0.917nm Bmax 32nM; lipid A30P α-syn mice neuron-specific binding signal that overlaps with α-syn pathology in the medium and brain stem of meaningful SUVR signal | ||||||
| Animal in vivo PET | mouse striatum → PET scan of (PFF mice and PFF NHP) (marmosette); (Ono, 2021 #2305) C11-MODAG-001 in the entered brain & midbrain sections compared to a... fight ASYN PFF in 'aged ASYP α-syn neuron-specific binding signal that overlaps with α-syn pathology in the medium and brain stem of MSA mouse SUVR signal | ||||||
| ARG / desirable PK characteristics in NHP | |||||||
| Preclinical Tox |
Two studies in rat (Accelead Study No. 22-058(ac); 9101%): cold study Non-radioactive bridging extended single i.v. (Accelead Study No. 22-080(ac); rats radiation, no observed adverse-finding by i.v. of [11C]C05-05; toxicity to attenuated. Objective of FH: Evaluate α-syn natural pathology Subjects: 7 healthy adults α-syn visual elevation of α-synuclein deposition by [11C]C05-05. PET: Three sessions over 120-min and two 30-min(s) of dynamic PET scans will be conducted of [11C]C05-05. Schedule: 1 month Preliminary Blood Screen Blood 12hrs sec must be examined on the day before [11C]C05-05. Result Onishi from Dr Matsuoka, who is a PI of the clinical study, it says that 1 of T-08 was successfully commenced on August 5th in one healthy subject and there has not been any problems reported. Scan in a patient is planned next month. | ||||||
| Protocol B-safety |
A-efficacy: synuclein deposition in DLB cases; even if these patients have presented patients with cerebellum α-binding when used to [11C]05-05 a similar density than other AD brains; in line with this notion Schedule: 1 month / Preliminary Blood Screen / Blood 12hrs sec scan-min 12hrs sec result (Matsuoka, 2022 #2127) | ||||||
| FH | F/H F/U studies will include test-retest SPAL Team (QST Eisai Ono and Takeda) did not finalize follow up studies whereas the dosing for the latest iteration of compound was discussed with Takeda PCC SPAL team in the framework of the SPAL collaboration; PD modal of investigation by FU. We will be discussed with US IND should be discussed with Takeda SPAL Team SPAL-T-S41 GPT, and Aiko Adam Schwarz at PTS Clinical Imaging → use TAK-341 study The team Nomura has left the team Onishi can overall leader, Takashi Wakabayashi chemistry leader | ||||||
| Four αSyn isomers | with selectivity issue, as shown below 20%, blocking with AD proteins, besides they never isolated Aβ & tau → FH 야 NK chemical modification 일정 | ||||||
Alzforum potential booster
- Lack of fluorine in MK-7337 prevents FOSO28 to [18F] isotope synthesis (short half life and can’t be used for larger multi-cool).
- (cO5-05 is too slow); a specific tyrosine residue—Y39—for (?)