AAN 2026 | Syn-Sleep & Syn-Q: skin biopsy detection of p-α-synuclein in RBD and Parkinson’s disease

So we’ve been really interested in what the skin can tell us about neurodegenerative disease for some time. And so these two studies are really looking at early disease evaluation. And so patients with REM sleep behavior disorder often will go on to develop a Parkinsonian syndrome or other neurodegenerative process over about 15 years or so. And so what we’re doing is actually taking skin biopsies from three locations on the body to really identify whether we can detect phosphorylated alpha-synuclein within the axons in the skin. And we think that this will really help us to understand the individual’s risk for developing a Parkinsonian syndrome and the time frame that that may occur. So the Syn-Sleep study is looking at rate of change over time of synuclein. It’s a longitudinal study. And what will happen, can we predict whether people with REM sleep behavior disorder will develop Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy. Now, the Syn-Q study is very similar. We’re looking at patients specifically now with Parkinson’s disease, and we’re doing six-month interval follow-ups and biopsies. And we’re looking to see whether there is a significant change in phosphorylated alpha-synuclein within the skin that will help us predict development of more severe disease because this is really going to be an important aspect for clinical trial development and whether we can actually establish a biomarker that is measurable and it can change over time. So they’re both ongoing. We do know that we have follow-up data we’re presenting at this conference and in both cases we see a significant increase in phosphorylated alpha-synuclein over time. So in the Syn-Sleep study, we see about a 30% increase in phosphorylated alpha-synuclein from the initial visit to 12 months later. And in the Syn-Q study in Parkinson’s disease, we see about a 10 to 12% increase over six months. Now that study’s ongoing and actually both are longitudinal with further follow-up planned, so we’ll be able to determine whether in the Syn-Sleep study anybody phenoconverts from RBD to either multiple system atrophy, dementia with Lewy bodies, or Parkinson’s disease, and whether the amount of synuclein and rate of change helps us to predict when that time course may occur. Similarly for the SynQ study, we’re looking to see whether there’s a rate of change over time in patients with Parkinson’s disease. And one of the things we found already is that patients with REM sleep behavior disorder and Parkinson’s disease have much greater peripheral alpha-synuclein deposition already. And so it suggests that at least on those individuals with RBD likely have the pattern of synuclein deposition that’s well described by Per Borghammer’s theory of brain first, body first, synuclein spread. The brain first is thought to go through the olfactory bulb into the brainstem and then descend, whereas the body first starts in the gut and then ascends and goes through to the central nervous system from there, which means that the periphery, the skin would be affected very early in the course. And that’s exactly what we’re seeing is that patients with REM sleep behavior disorder have a lot of peripheral synuclein and it helps predict development of these degenerative disorders.

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