Changes in Core Temperature Following Administration of FC5, a Blood-Brain Carrier Fused with Neurotensin in Mice, Rats and Non-Human Primates.
- 1Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, Canada.
- 2Biology Program, Division of Science, New York University Abu Dhabi, Saadiyat Island Campus, Abu Dhabi P.O. Box 129188, United Arab Emirates.
Abstract
Development of therapies and pharmacological management of central nervous system diseases is significantly hampered by the presence of the highly selective blood-brain barrier (BBB). Receptor-mediated transcytosis (RMT) has proven to be a robust mechanism for delivering a wide variety of therapeutic modalities across the BBB. The present study describes the use of a neurotensin-based pharmacodynamic model to evaluate the brain penetrating capacity of FC5, a well-characterized RMT shuttle. Here we produce fusion molecules of FC5 with human Fc and neurotensin and show that intact but not C-terminally clipped neurotensin proteins containing either FC5 (FC5Fc-neurotensin) or a non-BBB-crossing control (A20.1Fc-neurotensin) retain the ability to activate neurotensin receptor type 1. In in vivo studies, intravenous administration of FC5Fc-neurotensin, but not neurotensin alone or A20.1Fc-neurotensin, induced a drop in the core body temperature in both rats and mice. We further extended these findings to non-human primates, demonstrating the ability of FC5 to cross the BBB in this species. Collectively, our results further support the potential of FC5 in delivering payloads across the BBB. The neurotensin model of hypothermia is also validated as a pharmacodynamic approach for assessing brain delivery, albeit with some necessary considerations into the molecular characterization of fusion constructs before in vivo evaluation.
Related
- Changes in bone density and metabolism marker levels in type I Gaucher's disease following annual zoledronic acid hydrate administration: A case report
- Exacerbation of Pre-existing Hypothyroidism Following Enarodustat Administration in a Patient on Peritoneal Dialysis: A Case Report
- Ocular tissue distribution of Ocular Surface Immune Globulins Following Topical and Subconjunctival Administration: A Novel Strategy for Mitigation of ADC-Associated Ocular Toxicity
- Stepwise administration of de novo ketogenic parenteral nutrition for refractory epilepsy during prolonged bowel rest following duodenal perforation
- Successful Alternate-day Osimertinib Administration with Desensitization Following Osimertinib-induced Hepatotoxicity and Neutropenia in a Case of EGFR-mutant Lung Cancer
BibTeX
@article{yogi2026changes,
title = {{Changes in Core Temperature Following Administration of FC5, a Blood-Brain Carrier Fused with Neurotensin in Mice, Rats and Non-Human Primates.}},
author = {Alvaro Yogi and Etienne Lessard and Eric Brunette and Christie E Delaney and Arsalan S Haqqani and Anna Robotham and Wael Alata and Maria J Moreno and Danica B Stanimirovic},
journal = {Cells},
year = {2026},
month = sep,
doi = {10.3390/cells15191770},
url = {https://europepmc.org/article/MED/42882467},
note = {CC BY},
}
RIS
TY - JOUR
TI - Changes in Core Temperature Following Administration of FC5, a Blood-Brain Carrier Fused with Neurotensin in Mice, Rats and Non-Human Primates.
AU - Alvaro Yogi
AU - Etienne Lessard
AU - Eric Brunette
AU - Christie E Delaney
AU - Arsalan S Haqqani
AU - Anna Robotham
AU - Wael Alata
AU - Maria J Moreno
AU - Danica B Stanimirovic
PY - 2026
DA - 2026/09/29
JO - Cells
DO - 10.3390/cells15191770
UR - https://europepmc.org/article/MED/42882467
AB - Development of therapies and pharmacological management of central nervous system diseases is significantly hampered by the presence of the highly selective blood-brain barrier (BBB). Receptor-mediated transcytosis (RMT) has proven to be a robust mechanism for delivering a wide variety of therapeutic modalities across the BBB. The present study describes the use of a neurotensin-based pharmacodynamic model to evaluate the brain penetrating capacity of FC5, a well-characterized RMT shuttle. Here we produce fusion molecules of FC5 with human Fc and neurotensin and show that intact but not C-terminally clipped neurotensin proteins containing either FC5 (FC5Fc-neurotensin) or a non-BBB-crossing control (A20.1Fc-neurotensin) retain the ability to activate neurotensin receptor type 1. In in vivo studies, intravenous administration of FC5Fc-neurotensin, but not neurotensin alone or A20.1Fc-neurotensin, induced a drop in the core body temperature in both rats and mice. We further extended these findings to non-human primates, demonstrating the ability of FC5 to cross the BBB in this species. Collectively, our results further support the potential of FC5 in delivering payloads across the BBB. The neurotensin model of hypothermia is also validated as a pharmacodynamic approach for assessing brain delivery, albeit with some necessary considerations into the molecular characterization of fusion constructs before in vivo evaluation.
SN - 2073-4409
ER -