Australian company Syntara and Parkinson’s Research Ventures have reported early signs that a novel anti-inflammatory candidate may reduce brain inflammation in people at high risk of developing Parkinson’s disease.
In a randomised, double-blind, placebo-controlled Phase 2 trial of candidate SNT 4728 in 41 patients with isolated REM sleep behaviour disorder, the company observed a statistically significant reduction in putamen neuroinflammation after 12 weeks of treatment.
The putamen is a brain region linked to the motor symptoms of Parkinson’s, and the trial’s imaging showed a unilateral reduction in Translocator Protein (TSPO) signal in that region, with 20 of 30 patients receiving active treatment recording a reduction from baseline.
Broader analyses also identified additional areas of reduced TSPO signalling, including regions within the temporal lobe, while no statistically significant change was detected in other predefined regions, such as the substantia nigra, caudate or occipital cortex.
The study evaluated a once daily oral 15 mg dose chosen for its predicted target engagement in the brain based on prior clinical work and measured microglial activation using PET imaging alongside other biomarkers.
The enrolled cohort had features that enriched for progression risk, with a median age of 68 years, 93 per cent male, 90 per cent hyposmic or anosmic, and 95 per cent positive for misfolded alpha-synuclein in cerebrospinal fluid.
Professor Simon Lewis of Macquarie University put the findings in the context of studying people long before clinical Parkinson’s emerges.
Professor Lewis said, “SNT 4728 is being evaluated in a prodromal Parkinson’s population where progression to symptomatic disease is very slow and can take over a decade. Therefore, any measurable change over only three months of treatment is notable, and seeing a statistically significant reduction in TSPO signal in the putamen, a region central to motor symptoms, is encouraging and suggests the drug may be modulating disease-relevant neuroinflammatory pathways. The further imaging and biomarker analyses still to come from this study will help our understanding of the durability and clinical significance of this effect.”
Dr Lynsey Bilsland of Parkinson’s Research Ventures said, “Right now, no drug can stop or slow the progression of Parkinson’s. With SNT4728, Syntara have shown that they are able to modify a key process linked to Parkinson's progression through short-term treatment many years before Parkinson's is diagnosed. In this trial, participants gave their time in the hope of delivering something that will improve life with Parkinson’s for generations to come. Seeing such a high percentage of them have a positive response to the drug is encouraging and we look forward to reviewing the remaining results in the coming months as we continue our globally powered search for a cure.”
Syntara CEO Gary Phillips added, “This study pushes the boundaries of what is technically possible and, when complete, will amass a significant body of evidence in this world-first interventional study in iRBD. It would not have been possible without the support from Parkinson’s Research Ventures who funded the study, the dedication of our two principal investigators, Prof Simon Lewis (Sydney) and Prof Michele Hu (Oxford), and the healthcare teams at the sites and, of course, the patients. The study has generated a great deal of interest in the wider Parkinson’s community and we look forward to working with our collaborators to deliver the remaining trial results in Q3 2026 and evaluate the path forward after this promising start.”
Syntara said it has filed a provisional patent application based on SNT 4728’s activity in iRBD, and that full clinical, imaging, digital, and biological marker data will be available in the third quarter of 2026 to inform next steps in development and to assess the potential to slow progression from prodromal stages to symptomatic Parkinson’s.
