Indian Institute of Technology Madras researchers have found that energy deficiency in certain cells in the human brain to be a major cause for Parkinson’s Disease (PD), a neurodegenerative disorder. This research could lead to scientists and other stakeholders focusing on improving the efficiency of energy delivery to these cells, which might finally lead to a cure for PD.

Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss has not clearly been elucidated before. The IIT Madras researchers developed a computational model that showed that energy deficiency might be a major cause of SNc cell loss in Parkinson’s Disease.

This computational modelling was developed by Dr Vignayanandam Ravindernath Muddapu. The findings of this research have been published recently in the prestigious peer-reviewed International Journal Nature Scientific Reports.

Elaborating on the important findings of this research, Prof V Srinivasa Chakravarthy, Department of Biotechnology, IIT Madras, said, “While existing treatments manage PD symptoms – sometimes with great effect – a cure demands an understanding of the root cause of SNc cell loss. This is the main question addressed in our work: What is the major underlying cause of SNc cell loss in PD?”

Further, Prof V Srinivasa Chakravarthy said, “It is quite remarkable that loss of neurons in a small nucleus like SNc can have wide-ranging, devastating effects in all the four major domains of brain function – sensory-motor, cognitive, affective, and autonomous. The sequence of the three computational studies suggests that metabolic deficiency within the basal ganglia circuit is the common underlying factor at the subcellular, cellular, and network-level in PD. Thus, we have a reasonably comprehensive theory of the pathogenesis of Parkinson’s disease.”

This research was undertaken at IIT Madras Computational Neuroscience Laboratory, which aims to build a simplified model of the whole brain and use it to develop applications in medicine and engineering. Prof Chakravarthy is the head of Computational Neuroscience Laboratory.

The computational model showed that: At the subcellular level, metabolic deficiency leads to changes including alpha-synuclein aggregation, reactive oxygen species production, calcium elevation, and dopamine dysfunction, which are characteristic subcellular changes in Parkinson’s disease.

Building on the platform of this research, Prof Chakravarthy and his team plan to develop a therapeutic computational testbench for PD, wherein the proposed model of SNc will be the centre of a larger framework. This will link cellular-level dysfunctions to behavioural-level abnormalities.

Moving forward in the next five years, this type of framework will help in providing personalised medicine for PD patients rather than the currently employed trial and error approach, inform researchers.