Switching on a light to solve the puzzle - finding a Parkinson's cure PART 1

Imagine you are in a windowless room that is plunged in darkness and the task facing you is to complete a giant jigsaw puzzle; the puzzle, once completed, will form a cure for Parkinson's. It's a fiendish puzzle too because not all the pieces will fit and the final picture will change as you put pieces together. It is highly unlikely you will finish it by groping in the dark and randomly putting the jigsaw together; indeed you won't even know when you have finished if you can't see the pieces!

Luckily we humans have the scientific method that provides the batteries to power four different torches to illuminate the different pieces of the puzzle. There's a torch to see inside nerve cells, another to see what's happening in the brain, one to look in model organisms such as mouse and finally one to look in human patients.

All four torches must be brought together if there is any hope of solving the puzzle.

The Oxford Parkinson's Disease Centre (OPDC) at the University of Oxford recognises the value of this multi-torch approach. The OPDC brings together Consultant Neurologists, mouse geneticists, biologists who are experts in how the basal ganglia works (the part of the brain affected in Parkinson's) and cell biologists to ensure the flow of knowledge from genes to nerve cell to brain to patient is as complete as possible; the intensity of light from four torches is higher than any one torch alone.

From patients...

The first piece of the puzzle that needs to be laid down is an accurate definition of Parkinson's disease. This provides the necessary context for all research and frames the target that a cure needs to aim for. Such a comprehensive definition will also help to identify individuals with Parkinson's before the emergence of symptoms (someone diagnosed today has already lost about 70% of dopamine producing nerve cells in the sustantia nigra). Dr Michelle Hu, a Consultant Neurologist, is leading a major effort to recruit 1000 Parkinson's patients in the Thames valley area (and subjecting them to a wide range of movement, behavioural and cognitive tests) to understand the disease in greater detail. It is hoped that the data generated can also address a crucial question: are the many and highly variable symptoms currently grouped together as Parkinson's disease in fact several diseases? This could prove vital to work out if there is more than one jigsaw puzzle to solve.

A related aim of the study is to find so called biomarkers (i.e. signs of the disease expressed by the body possibly up to 15 years before symptoms emerge). Currently there is no presymptom or diagnostic test for Parkinson's. Dr Hu presented two promising approaches; preliminary data shows that cells in the gut in some Parkinson's sufferers have the same accumulation of protein (called alpha synuclein) that is seen in nerve cells that die in the brain of sufferers. Gut cells are easier to analyse and if the accumulated protein is present in the gut it is likely to also be in the brain where it will eventually cause Parkinson's. Therefore, identifying diseased gut cells before movement symptoms occur will enable earlier intervention to improve quality of life.

A less invasive and potential large scale approach could be to record a person's voice online or over the telephone and a computer program would look for any early signs of tremor in the vocal cords. This could revolutionise and simplify diagnosis.

SEE PART 2 TOMORROW!

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OPDC http://opdc.medsci.ox.ac.uk/