Case Study: Disease Model Phenotyping and Efficacy Assessment for Neurodegenerative Disorders
Discover a unique approach for developing effective therapies
In this case study, readers can hear about a novel approach for in vivo, longitudinal imaging of neural circuit activity and amyloid-beta plaque pathology in Alzheimer’s disease mouse models. This case study discusses the benefits of this method for enhancing preclinical drug development by providing more sensitive and translationally relevant assays for therapeutic assessment.
Readers can expect to learn more about:
- Bruker’s Inscopix solution enables direct measurement of neural activity and disease pathology in live animals
- The benefits of imaging neural circuit activity in disease-relevant regions
- How sensitive and translationally relevant assays excel over traditional histopathology or in vitro pharmacology
- The Inscopix Discovery Lab offers both standardized and custom neurobehavioral studies
The Need
To discover the next generation of more effective therapies, neuroscientists need better preclinical assays that transcend the well-established shortcomings of both histopathology and in vitro pharmacology and are more predictive of clinical performance.
The Approach
Preclinical efficacy assessments typically rely on histopathology and in vitro pharmacology, which are poor predictors of treatment response in the complex environment of the intact and active brain.
We take a different approach
Bruker’s Inscopix solution combines in vivo brain imaging and behavior to provide a deep understanding of how disease pathology and candidate treatments impact neural circuit function in the intact brain during active behavior, informing early and decisively on questions that are critical to a successful preclinical program. This includes critical insights into target engagement, dosefinding, pharmacodynamics, efficacy, lead candidate selection, and more.
Key Benefits
- In vivo, in-brain measurement of neural activity and disease pathology (e.g., Aβ plaques)
- Direct readout from therapeutically targeted circuits
- In-life measure enabling within-subject study design
Case Study: Alzheimer’s Disease Neural Circuit Phenotype
Modeling Aβ plaque pathology for therapeutic development
Traditional preclinical efficacy assessments for Alzheimer’s disease (AD) require large numbers of animals and have shown limited predictive value for clinical outcomes. To advance the development of effective therapeutics, there is a critical need for more sensitive and translationally relevant assays that can provide in-life tracking and quantification of disease pathology and its impact on neural circuit function and behavior. This study aimed at developing a novel preclinical assay for AD therapeutic development using longitudinal in vivo brain imaging of amyloid-beta (Aβ) plaques and neural circuit dynamics.
Methods
Mouse Moudel
- Proprietary AD model and WT littermates
Brain Region
- Primary Motor Cortex (M1)
Cell Type
- Pyramidal neurons
Age
- 10-15 months
Approach
- Dual-color headmounted miniature microscope (nVue2.0) to perform longitudinal in vivo imaging of neural circuit activity and Aβ plaque development
Impact and Applications
- Primary motor cortex in AD mice exhibit impaired neural activity patterns, reflecting plaque-driven circuit dysfunction.
- These findings can now be leveraged as a circuit-based assay for testing Alzheimer’s therapies in a biologically meaningful, functional context.
- Such an assay could be particularly valuable for assessing monoclonal antibodies, demonstrating not only plaque clearance but also restoration of neural circuit function.
Transform your neuroscience drug development
The Inscopix Discovery Lab is a state-of-the-art in vivo rodent R&D facility and a team of neuroscientists and brain imaging and behavior experts. We conduct fee-for-service contract research studies in support of preclinical programs, offering several standardized assays as well as custom neurobehavioral studies designed in collaboration with our clients. Contact us for more information to find out how we can meet the needs of your drug discovery programs.
