In Vivo Evaluation of RMT-Targeting Biologics
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In Vivo Evaluation of RMT-Targeting Biologics

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The delivery of biologics to the central nervous system (CNS) is significantly limited by the blood-brain barrier (BBB), which restricts the entry of macromolecules. Receptor-mediated transcytosis (RMT) uses endogenous transport mechanisms to facilitate the targeted delivery of biologics across brain endothelial cells. In the development of RMT-targeting biologics, in vivo evaluation is a critical step to validate the success of targeting strategies and to ensure effective delivery of therapeutic payloads across the BBB. While in vitro assays provide valuable preliminary insights into binding, uptake, and transcytosis mechanisms, in vivo studies are essential to confirm these properties under physiological conditions, including systemic circulation, BBB transport, and biodistribution within the CNS.

A brain shuttle antibody for Alzheimer's disease that exhibits reduced peripheral effector function as a result of its inverted binding mode.
Fig. 1 A brain shuttle antibody for Alzheimer's disease that exhibits reduced peripheral effector function as a result of its inverted binding mode. (Weber, et al., 2018)

Our Services

At Ace Therapeutics, we are committed to advancing the preclinical development of RMT-targeting biologics through in vivo evaluation services. Our in vivo evaluation platform is designed to help clients assess the pharmacokinetics, brain biodistribution, and therapeutic efficacy of their RMT-targeting biologics. Whether you're developing therapeutic monoclonal antibodies, therapeutic peptides, therapeutic recombinant proteins, or gene therapies, our services aim to help de-risk and accelerate your CNS targeting programs.

Our In Vivo Evaluation Services

Services Description
Biodistribution and Pharmacokinetics (PK) Studies We can conduct in vivo PK and biodistribution studies to evaluate the brain delivery efficiency of RMT-targeting biologics.
PK Analysis of RMT-Targeting Biologics
  • Plasma and brain PK profiles after intravenous (IV) or alternative routes of administration
  • Calculation of key PK parameters, e.g., Cmax, Tmax, AUC, clearance, volume of distribution, half-life
  • Extended brain exposure
Assessment of Brain Distribution and Uptake of RMT-Targeting Biologics
Quantitative assessment of the concentrations of RMT-targeting biologics in brain lysates or confirmation of brain distribution using imaging techniques. Available methods include:
  • ELISA-based bioanalysis
  • Fluorescence or radiolabel tracking
  • Positron Emission Tomography (PET) imaging for real-time in vivo visualization
Efficacy Studies in Animal Models We offer customized efficacy evaluation services for RMT-targeting biologics in disease-relevant animal models, particularly those modeling CNS disorders such as Alzheimer's disease, stroke, Parkinson's disease, and neuronopathic lysosomal enzyme disorders. Assessment endpoints include:
  • Survival and disease progression metrics
  • Behavioral and cognitive tests
  • Histopathological and immunohistochemical analysis
  • Biochemical and molecular readouts

Advantages of Our Services

  • Specialized expertise in neuro-PK, including detailed analysis of RMT-targeting biologics in whole brain, brain microvessels, brain extracellular fluid, and brain parenchyma.
  • Rigorous quantification techniques to assess true brain uptake and exclude vascular interference.
  • Flexible modality options for pharmacokinetics, biodistribution, and brain uptake studies of RMT-targeting biologics.
  • Comprehensive in vivo models of CNS diseases for efficacy evaluation.
  • End-to-end project support, from experimental design to data analysis and interpretation.

Ace Therapeutics' in vivo evaluation platform is designed to accelerate the development of CNS-targeted biologics by providing reliable data on pharmacokinetics, brain exposure, and therapeutic efficacy. We are committed to supporting our clients in advancing their RMT-targeting biologics with confidence. Contact us today to learn more about our RMT-based brain drug delivery services.

Reference

  1. Weber, F., et al. (2018). Brain shuttle antibody for Alzheimer's disease with attenuated peripheral effector function due to an inverted binding mode. Cell reports, 22(1), 149-162.
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