Understanding Parkinson’s disease – lessons from biology
The problem
Parkinson's disease is a common neurodegenerative disease that afflicts more than 2 per cent of people aged over 75 years. In the UK, this means there are over 100 000 people with the disease: with the ageing population this number will increase. The annual cost in nursing-home care for Parkinson's disease alone in the UK is estimated to be about £600-800 million.
Despite tremendous progress in the identification of genes associated with Parkinson’s and related disorders over the last decade, there is still only outline and sketchy information about the molecular pathways involved, and their constituents and their interactions.
Finally, in order to really understand the pathway to human disease, and to be able to influence its progression, the earliest phase needs to be examined. Thus the consortium will also focus on developing understanding of the very early symptoms or warnings of the illness.
The questions
The consortium hypothesises that there are multiple causes of Parkinson's, which result in a very small number of separate but converging biochemical pathways. These pathways interact with the molecular pathology of ageing and induce neuronal dysfunction and death, producing the characteristic pathological features of the condition.
It will need to identify all the significant genetic risk factors, and place these molecules and their variants in their pathways to enable it to understand how the human disease begins and develops.
To understand these pathways and mechanisms requires the establishment and integrated use of a range of models.
The research programme
The consortium aims to achieve a much fuller picture of all the major genetic factors that underlie Parkinson's. It will then identify and characterise the biochemical pathways that these genes determine, and explore their role in the development of disease. To dissect these mechanisms, the consortium has brought in expertise from mitochondrial biology, cell signalling and Drosophila biology to complement its other model systems.
In parallel it will study the very earliest stages of the illness. It is widely believed that only by understanding these early phases will we be able to modify the disease course for the greatest clinical impact. To aid this work, the consortium has harnessed the clinical and biochemical resources of the national Gaucher's disease clinic. This will help it to build cohorts of individuals who are genetically at risk; detailed studies of these individuals will include imaging and biochemical assessments.
Over the next five years, the consortium’s plan is to produce detailed knowledge of the molecular pathways that lead to Parkinson’s, and validated markers of its evolution.
The team
Principal Investigators
University College London (Institute of Neurology)
- Nicholas Wood
- John Hardy
- Anthony Schapira
Co-Investigators
University of Dundee
- Dario Alessi (MRC Protein Phosphorylation Unit)
University of Sheffield
- Alex Whitworth (MRC Centre for Developmental and Biomedical Genetics)
University College London
- Andrey Abramov (Institute of Neurology)
- Kailash Bhatia (Institute of Neurology)
- J Mark Cooper (Institute of Neurology)
- Michael Duchen (Dept of Physiology)
- Derralyn Hughes (Royal Free)
- Andrew Lees (Institute of Neurological Studies)
- Atul Mehta (Royal Free)
- Tamas Revesz (Institute of Neurology)
- Jan-Willem Taanman (MRC Centre for Neuromuscular Diseases)
- Tarek Yousry (MRC Centre for Neuromuscular Diseases)