As demonstrated here in healthy animal models, PBT434 can demonstrate target engagement in those models.
[We postulated that if the ability of PBT434 to prevent the elevation in α-synuclein levels following MPTP in wild type mice was due to its effect on the labile iron pool, that same effect might also be detectable in healthy animals. Examination of samples of post-mortem CSF from healthy dogs treated with PBT434 for 28 days showed a significant dose-dependent reduction in α-synuclein, an effect also observed in rats fitted with an indwelling ventricular catheter, consistent with the hypothesis that PBT434 modulates α-synuclein expression at the translational level. This finding raises the possibility that CSF α-synuclein may be of value as a marker of target engagement in the clinical setting. There is considerable debate and some justifiable skepticism surrounding the use of biomarkers like CSF α-synuclein as indices of disease progression [
52], however, such biomarkers, especially if they are demonstrably linked to drug mechanism of action, may be judiciously applied to the evaluation of target engagement for new drugs, assisting in the early phases of clinical development.]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490188/
Phase1 trials are just about safety, but the good safety results will be much more valuable IMO if they can demonstrate target engagement, especially to prospective partners. When you consider the PBT2 IMAGINE AD trial was about demonstrating target engagement, it is a big deal if target engagement can be demonstrated at phase 1 level trials for PBT434 in PD, and thanks to the dedicated world class scientists at the Florey, it looks like they have found a way.
"PBT434 modulates α-synuclein expression at the translational level. " I looked "translational level" up and the meaning is generally like at the level of the RNA signal from the gene.
MPTP mouse models "Among the most widely used models of Parkinson’s disease (PD) are those that employ toxins, especially 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Depending on the protocol used, MPTP yields large variations in nigral cell loss, striatal dopamine loss and behavioral deficits. Motor deficits do not fully replicate those seen in PD. Nonetheless, MPTP mouse models mimic many aspects of the disease and are therefore important tools for understanding PD."
Just my opinion as a private investor. Also am not a medical professional.
