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Preclinical characterization and IND-enabling safety studies for PNT001, an antibody that recognizes cis-pT231 tau.
Foster, Kelly; Manca, Matteo; McClure, Kim; Koivula, Pyry; Trojanowski, John Q; Havas, Daniel; Chancellor, Sarah; Goldstein, Lee; Brunden, Kurt R; Kraus, Allison; Ahlijanian, Michael K.
Afiliación
  • Foster K; Pinteon Therapeutics, Inc., Discovery Biology, Newton, Massachusetts, USA.
  • Manca M; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • McClure K; Pinteon Therapeutics, Inc., Discovery Biology, Newton, Massachusetts, USA.
  • Koivula P; Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Trojanowski JQ; Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Havas D; Psychogenics, Inc, Biology Paramus, New Jersey, USA.
  • Chancellor S; Molecular Aging & Development Laboratory, Boston University School of Medicine, USA.
  • Goldstein L; Molecular Aging & Development Laboratory, Boston University School of Medicine, USA.
  • Brunden KR; Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Kraus A; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Ahlijanian MK; Pinteon Therapeutics, Inc., Discovery Biology, Newton, Massachusetts, USA.
Alzheimers Dement ; 19(10): 4662-4674, 2023 10.
Article en En | MEDLINE | ID: mdl-37002928
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Tauopatías Límite: Animals / Humans Idioma: En Revista: Alzheimers Dement Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Tauopatías Límite: Animals / Humans Idioma: En Revista: Alzheimers Dement Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos