Parkinson’s trigger in focus for new international research

A three-year grant from the Aligning Science Across Parkinson’s initiative will support the most in-depth look at the cellular mechanisms that lead to Parkinson’s disease to date.

Leading researchers from the USA and Garvan will use cutting-edge technology to reveal the complex interplay of genes, molecules, cells and age-related factors that trigger Parkinson’s disease, a debilitating neurodegenerative condition that is estimated to affect more than 10 million worldwide, but for which there is no known cause.

Through a significant US$8.95 million grant from the Aligning Science Across Parkinson’s initiative, a global collaboration between Memorial Sloan Kettering Cancer Center, the New York Stem Cell Foundation Research Institute, Harvard University, the University of Illinois and the Garvan Institute of Medical Research, will link genomic ‘networks’ with the cellular risk factors that lead to Parkinson’s disease.

“Our research will help solve how genomics and cellular mechanisms work to cause Parkinson’s,” says A/Prof Joseph Powell, Director of the Garvan-Weizmann Centre for Cellular Genomics, who is leading the project’s efforts at the Garvan Institute.

“In brain cells developed from normal and patient-derived induced pluripotent stem cells (iPS cells) in cell culture, we will investigate how genomics and the ‘second hit’ risk factors – the interplay of different brain cells and ageing – shape individual disease risk. We hope this new understanding will enable early diagnosis and prediction of therapeutic targets that could halt or reverse the disease, and identify subgroups of Parkinson’s that could be therapeutically meaningful.”

Parkinson’s risk: a new perspective

Parkinson’s is a debilitating, progressive disease that affects the control of body movements as well as a range of other non-motor conditions that differ amongst patients diagnosed with Parkinson’s. It is characterised by degenerative processes in the brain that cause tremors that may eventually lead to stiff limbs, a severely compromised posture and the inability to carry out activities independently over time.

“We know there are large numbers of gene variants that can predispose an individual to Parkinson’s, and people carry different combinations, such that not every person who carries them is affected by disease, or has the same symptoms. This means there are other risk factors that contribute to disease development,” says A/Prof Powell.

Researchers will use data from Parkinson’s patients, iPS cell technologies, state-of-the-art cellular genomics approaches and sophisticated computational methods to study ‘second hit’ risk factors. These include the interactions between different gene variants, different brain cells and factors related to age.

“Using engineered human iPS cells and a high-throughput approach, we will construct a genomic network that links gene variants associated with Parkinson’s risk to cellular factors,” says A/Prof Powell.

On a mission to stop Parkinson’s

“There are no current treatments for the causes of Parkinson’s, in part because we have a poor understanding of how and why the disease develops,” says Dr Lorenz Studer, who will lead the project at the Memorial Sloan Kettering Cancer Center. “A more detailed understanding of Parkinson’s risk will help distinguish different subtypes of the disease, and may help improve the diagnosis and treatments of individual patients.”

Lead researchers of the project are Joseph Powell (Garvan Institute), Lorenz Studer (Memorial Sloan Kettering Cancer Center), Gist Croft (New York Stem Cell Foundation Research Institute), Vik Khurana (Brigham and Women’s Hospital and Harvard Stem Cell Institute) and Jian Peng (University of Illinois at Urbana-Champaign).

At the Garvan Institute, the project will be carried out in association with the Australian Parkinson’s Mission (APM), a collaborative research and clinical trials program largely funded by the Medical Research Futures Fund, that aims to slow, stop and cure Parkinson’s disease. The APM is a partnership between the Garvan Institute, the University of Sydney, Shake It Up Australia Foundation, the Cure Parkinson’s Trust (UK), The Michael J. Fox Foundation (USA) and Parkinson’s Australia.

The Aligning Science Across Parkinson’s initiative aims to advance targeted basic research for Parkinson’s. The Michael J. Fox Foundation for Parkinson’s Research is the ASAP implementation partner and issued the grant.

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