QSP Programs

Neurodegenerative Diseases

Neurodegenerative diseases (ND), such as amyotrophic lateral sclerosis (ALS), Parkinson’s, Alzheimer’s, and Huntington’s disease are devastating, incurable diseases that affect over 7 million people in the US alone.  The exact cause of ND is largely unknown, though in Huntington’s Disease a single mutation in the huntingtin gene manifests the disease.  Epidemiological studies have long implicated traumatic brain injury (TBI) as a major risk factor for future development of neurodegeneration, dementia, and Alzheimer’s disease (AD).  Among different ND similarities exist in the disease pathophysiology, and it is reasoned that understanding one disease will shed light on understanding the other diseases, eventually leading to effective treatments.

The Quantitative Systems Pharmacology (QSP) approach is well suited to determine the molecular pathogenesis of ND.   In collaboration with Dr. Okonkwo in the department of Neurological Surgery and Dr.  Kochanek in the department of Critical Care Medicine we are applying QSP to advance our understanding of disease mechanism and to identify potential therapeutic targets in post-TBI neurodegeneration, and in collaboration with with Dr. Bahar in the department of Computational and Systems Biology, Dr. Friedlander in the department of Neuroscience, and the National Center for Advancing Translational Sciences (NCATS) we have implemented QSP to understand the molecular pathogenesis of selective neuronal toxicity in Huntington’s Disease.   In the latter collaboration, we have identified several molecules which are the basis of computationally identifying key pathways and networks involved in protecting neuronal cells from mutant huntingtin dependent cell death in Huntington’s Disease.

 

Pei, F., et al., Sci Rep, 2017