Preclinical characterization and IND-enabling safety studies for PNT001, an antibody that recognizes cis-pT231 tau
- Alzheimers Dement. 2023 Oct;19(10):4662-4674. doi: 10.1002/alz.13028.
- 1. Pinteon Therapeutics, Inc., Discovery Biology, Newton, Massachusetts, USA.
- 2. Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
- 3. Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- 4. Psychogenics, Inc, Biology Paramus, New Jersey, USA.
- 5. Molecular Aging & Development Laboratory, Boston University School of Medicine, USA.
Background: The cis-conformer of tau phosphorylated at threonine-231 (cis-pT231 tau) is hypothesized to contribute to tauopathies. PNT001 is a humanized, monoclonal antibody that recognizes cis-pT231 tau. PNT001 was characterized to assess clinical development readiness.
Methods: Affinity and selectivity were assessed by surface plasmon resonance and enzyme-linked immunosorbent assay. Immunohistochemistry (IHC) was performed with brain sections from human tauopathy patients and controls. Real-time quaking-induced conversion (RT-QuIC) was used to assess whether PNT001 reduced tau seeds from Tg4510 transgenic mouse brain. Murine PNT001 was evaluated in vivo in the Tg4510 mouse.
Results: The affinity of PNT001 for a cis-pT231 peptide was 0.3 to 3 nM. IHC revealed neurofibrillary tangle-like structures in tauopathy patients with no detectable staining in controls. Incubation of Tg4510 brain homogenates with PNT001 lowered seeding in RT-QuIC. Multiple endpoints were improved in the Tg4510 mouse. No adverse findings attributable to PNT001 were detected in Good Laboratory Practice safety studies.
Discussion: The data support clinical development of PNT001 in human tauopathies.
-
Cat. No.Product NameDescriptionTargetResearch Area
-
target: Tau ProteinResearch Areas: Neurological Disease