How to obtain the most value out of your neurodegenerative disease research models? 

To date, large ongoing efforts are being made to provide well-characterised animal models which are suitable for investigating novel therapeutics. To ensure full confidence in the efficacy profile of novel therapeutic agents, efficacy testing often needs to be performed in a selection of multiple models. In general, the choice of neurodegenerative mouse model can further depend on: 

• Pathophysiological relevance of the model, expression patterns of disease-associated fibrils/plaques/protein aggregates, degree of neuroinflammation, presence of cognitive deficits and/or motor deficits  
• Age at onset and progression of pathology  
• Availability and cost of models  

InnoSer’s expert neurology research team has characterised multiple neurodegenerative disease research models and can help advise which model is the most suitable for your research. 

InnoSer’s well-characterised Alzheimer’s disease models consist of several transgenic mouse models of Aβ plaque pathology, Tau pathology, and induced Tau models (patient-derived Tau or recombinant seeds). The biological and behavioral phenotypes make transgenic amyloid mice a valuable model of Alzheimer’s disease and suitable for drug-screening studies (Boedrich et al., 2018). In contrast to amyloid models (Figure 2) models with Tau pathology may also be highly relevant for frontotemporal dementia and other tauopathy diseases research (Figure 3).  

FIGURE 1. Transgenic amyloid models show robust cognitive impairments. Our sensitive CognitionWall™ Discrimination learning task not only detects learning impairments at 6 months (Remmelink et al 2016), but already at the age of 3 months in APP/PS1 mice, when deficits in the other common cognitive tests such as Morris Water Maze are not evident yet. At 16 weeks, this deficit in discrimination learning can be rescued by an acute dose of the BACE1 inhibitor LY2886721.  

FIGURE 2. Transgenic P301S (PS19) mice show Tau pathology (AT8) at 8 months of age in the hippocampus (HPC) and somatomotor cortex (SMCx).  

InnoSer’s well-characterised Parkinson’s disease models range from induced (MPTP, 6-OHDA, alpha-synuclein seeding with patient-derived or recombinant seeds), transgenic (alpha-synuclein, GBA, LRKK2). Different models can be used to model each of the distinct disease pathophysiology, such as the degeneration of dopaminergic neurons and associated neuroinflammation (Figure 3).  

InnoSer’s well-characterized ALS mouse models such as the SOD1, TDP-43 transgenic (Figure 4) and patient or recombinant-seeding models provide a translationally relevant platform for testing novel ALS-targeted therapies.  

Sample sizes, study timelines and the range of readouts used to establish the efficacy profile of your novel therapeutic agent highly differ between each model used. Contact us to obtain more example data, personalised advice on model selection or study timelines now.   

Before commencing efficacy studies, histopathology analyses can be performed to evaluate target engagement ex vivo using human brain slices via InnoSer’s sister company Connected-Pathology. Evaluating the therapeutic efficacy and translational potential of your novel compound is aided by determining the relationship between PK/PD parameters. Curious to learn more about InnoSer’s capabilities within the drug development space?