A Fresh Look at Parkinson’s Disease

Peter Wellstead
Adjunct Professor
Hamilton Institute, NUIM
Maynooth
County Kildare
Ireland

Parkinson’s disease (PD) presents enormous research challenges, so that 200 years after Parkinson’s defining essay, we still do not know the causes, nor can we cure it. PD is particularly difficult because it is not a disease in the classical sense - it is a systems disorder associated with a range of multi- factorial mechanisms and disease pathways. As a result the vulnerability to PD depends upon a number  f issues that can occur in many combinations and with various levels of genetic predisposition. Conventional disease research was not designed to deal with such diversity - a new perspective is required.

This seminar describes a fresh look at PD in the form of a systems approach involving mathematical modelling, computer-based simulation and analysis of disease dynamics. The central idea is to: (i) develop an integrative framework for consolidating and quantifying knowledge; (ii) use simulation and analysis to accelerate and focus experimental research. The seminar describes how this can be done for the two key phases of PD:

1. The lead up to PD (the presymptomatic phase)

2. The initiation of PD within a neuron (pathogenesis).

By providing a unifying framework for PD, we increase our understanding of a condition where many isolated facts are known but few links have been made. In particular, an integrative look brings two novel ideas: an energy deficit theory for neural vulnerability to PD, and the theoretical prediction of a neurochemical trigger – the Parkinson’s switch – responsible for pathogenesis.