Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB): A Translational Pharmacodynamic Biomarker for PIKfyve Inhibition With VRG50635 - PubMed
3 days ago
- #GPNMB
- #PIKfyve inhibition
- #ALS
- GPNMB investigated as a pharmacodynamic biomarker for PIKfyve inhibition.
- VRG50468 (active metabolite of VRG50635) shows significant response in cells, CNS, and peripheral tissues.
- Studies conducted ex vivo, in vitro, in animals, and in clinical settings.
- VRG50635 is a PIKfyve inhibitor pro-drug for ALS treatment.
- Peripheral pharmacology evaluated in PBMCs from healthy volunteers and mice.
- Central pharmacology assessed in ALS patient-derived motor neurons and mouse brains.
- Clinical studies in healthy adults examined plasma, PBMCs, and cerebrospinal fluid.
- GPNMB upregulation demonstrated across preclinical and clinical studies.
- Response to VRG50468 observed in rodent and human PBMCs and neurons.
- GPNMB induction was concentration, time, dose, and treatment duration dependent.
- GPNMB identified as a robust translatable PD biomarker for VRG50635 trials.