Developing a novel unsupervised and normalization-free tool for multi-omics integration and biomarker identification
Modeling Neurofilament trafficking in neurodegenerative disorders
- Area
- Systems Pharmacology
- Expertise
- Biomarker identification
- Modeling & simulation
Challenge
Develop a Quantitative System Pharmacology (QSP) model to evaluate the potential of neurofilaments as early biomarkers of disease onset and treatment response in patients with different neurodegenerative disorders, such as Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA), and Multiple Sclerosis (MS).
What we did
The model was implemented as a set of Ordinary Differential Equations (ODEs) describing the trafficking of neurofilaments from the nervous system to the periphery. In addition to literature data, proprietary data have been considered to calibrate the model in several treatment conditions. The model was finally validated by assessing its capability in reproducing a set of treatment scenarios not considered for model calibration.
Outcome
The good predictive performance of the model makes it a valuable tool for investigating neurofilaments as biomarkers of disease progression and treatment response in different neurodegenerative disorders and for in silico evaluation of novel treatment protocols.
Partner
Biogen, founded in 1978, is one one of the world’s first global biotechnology companies, leading innovative scientific research with the goal to defeat devastating neurological diseases.
https://www.biogen.com/An age-dependent mathematical model of neurofilament trafficking in healthy conditions
Paris A, Bora P, Parolo S, Monine M, Tong X, Eraly S, Masson E, Ferguson T, McCampbell A, Graham D, Domenici E, Nestorov I, Marchetti L, An age-dependent mathematical model of neurofilament trafficking in healthy conditions, CPT Pharmacometrics Syst Pharmacol. 2022;00:1-11. https://doi.org/10.1002/psp4.12770