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MDS 2022 | Lipidomic approaches identify Parkinson’s disease-specific lipid signatures

Serge Przedborski, MD, PhD, Columbia University Irving Medical Center, New York, NY, provides an overview of the ongoing research investigating lipid alterations in Parkinson’s disease. Lipidomic approaches have been used to screen a large number of lipids quickly to gain an understanding of the lipid alterations present and potentially find a signature characteristic of Parkinson’s disease but not of other conditions. Indeed, lipidomic studies have shown that a number of lipids content are altered in tissue or blood. Future research will focus on understanding the significance of those alterations to the pathophysiology of the disease. This interview took place at the 2022 International Congress of Parkinson’s Disease and Movement Disorders in Madrid, Spain.

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Transcript (edited for clarity)

I think that we really at the crossroad now, in part because of the advance in technology, we were able to move, I would say, reasonably quickly of course. It’s never quick enough for patients, but for us in the lab, it’s moving quite quickly. Part of the work has been, first, to try to determine what are the alterations that we see to then subsequently guide the type of investigations that we can do to try to refine our understanding of the alterations of lipid metabolism...

I think that we really at the crossroad now, in part because of the advance in technology, we were able to move, I would say, reasonably quickly of course. It’s never quick enough for patients, but for us in the lab, it’s moving quite quickly. Part of the work has been, first, to try to determine what are the alterations that we see to then subsequently guide the type of investigations that we can do to try to refine our understanding of the alterations of lipid metabolism.

So many investigators in Australia, in England, different part of Europe and the US and Asia, we have started to look using unbiased technique first, like lipidomics for example, to be able to screen quickly a large number of lipids. And have an understanding of what could be the alterations, the directionality, it’s important, some are increased, some are decreased. And basically the first step has been for us and many others to try to understand is there a signature that it’s characteristic of Parkinson’s versus any other disease or control conditions.

We have done that in tissue and like others, we have moved now to fluids. And indeed, what we see is that a number of lipids see their content in tissue or in blood altered. And so now the questions become the next step, which is that those alterations are great. They can be detected, they’re reproducible, many groups fortunately find maybe not identical alterations, but very similar alterations, which is comforting. But the question now, which is the tricky one, is what all that means. Are these alterations simply signature of something or is telling us more about how and why specific cells are dying in Parkinson’s disease for example. And so that’s where we have to return things that we have done for years to cell system or small animal models to try to modify, to replicate those alterations and see if they have some kind of pathogenic significance. And that’s of course, much longer and tedious work than identify the signature.

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Disclosures

Editor of eLife, Luciole Pharmaceuticals