Oxford University is to lead a major global research project into Parkinson’s disease, it has been announced.
Some £6.6 million has been set aside for the project.
It is the first time the institution will lead an Aligning Science Across Parkinson’s (ASAP) initiative and the announcement also heralds the only UK-led ASAP project this year.
The landmark collaboration with scientists from Boston University, USA, the Karolinska institute, Sweden, Peking University and Stanford University, will map, on an unprecedented scale, the original brain circuits that are vulnerable to Parkinson’s.
The team, led by Professor of Neuroscience Stephanie Cragg, aims to fully map out a key set of the neuronal circuitry relevant to Parkinson’s and they will assess how circuit activity changes during progression of Parkinson’s and define how dysfunction in vulnerable circuits relates to disease symptoms.
It will focus particularly on the circuits that govern dopamine output because the loss of dopamine in Parkinson’s is believed to be primarily responsible for increasing inability to select, tune and produce movements.
“We know dopamine neurons die, and that the messages they transmit on to other cells are lost in Parkinson’s, but we don’t really understand how all the other interacting circuits contribute to that and either make it worse or attempt to offset it,” said Professor Cragg. “So, we are looking to identify the sequence of dysfunction.”
Previous research has shown that affected dopamine neurons have uniquely large axon arbours, which form the most branched of all central nervous system neurons documented to date.
“It means that these axons have huge biological relevance in dopamine signalling because a large number of other systems can talk to these axons with the potential to powerfully transform dopamine output,” said Professor Cragg.
“The message emerging from dopamine axons can be tweaked along the way by lots of different things acting on these incredible axons.”
“With more than 99% of the neuron comprising these unusually large axon trees, we focused our ASAP grant on systematically defining the neuromodulators and circuits that are talking to dopamine axons.
“We will also compare whether these mechanisms are different in brain regions that are dying in Parkinson’s compared to brain regions that are resistant, to see if there are circuits that might make good targets for future therapies that could fix the vulnerable neurons but leave the resistant ones unaffected.”
The ASAP funding will allow the researchers to work on an unprecedented international collaborative scale.
Dr Ekemini Riley, ASAP managing director, said: “We are proud to partner with the University of Oxford on this innovative and impactful project that will position the field closer to new treatments for the millions living with and at risk of Parkinson’s disease.”
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