An experimental treatment being developed by Syntara improved movement in people at high risk of developing Parkinson's disease, and the benefit held for three months after treatment stopped, according to new results from a Phase 2 trial.
Syntara has announced that participants with isolated REM sleep behaviour disorder (iRBD) who took SNT-4728 showed a statistically significant difference in clinician-assessed motor signs compared with placebo at week 24. That point came 12 weeks after treatment ended.
iRBD is a sleep disorder associated with a high risk of progression to Parkinson's disease and related synucleinopathies.
Principal investigator Professor Simon Lewis of the Macquarie University Brain Institute and Clinic is presenting the findings today at the Clinical Breakthroughs Plenary Session of the International Congress of Parkinson's Disease and Movement Disorders in Seoul.
The trial enrolled 41 people with iRBD. They were randomised 3:1 to receive SNT-4728 or placebo for 12 weeks, and neither participants nor investigators knew who received which. The drug is designed to reduce brain inflammation by inhibiting two enzymes, MAOB and SSAO.
Researchers measured motor function with Part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale. Clinicians use this scale to assess slowness of movement, rigidity, tremor, gait and postural stability.
At the end of the 12 week treatment period, people taking SNT-4728 had slightly better motor scores than at baseline, while scores in the placebo group had worsened. By week 24, the treated group had improved further, and the placebo group had continued to decline. Syntara said the decline in the placebo group was in line with published studies of people with iRBD. The company said the stable scores in the treated group, both during treatment and afterwards, suggest a lasting clinical response from the drug's anti-inflammatory and antioxidant effects.
The motor findings add to imaging results Syntara reported in July. PET scans then showed a statistically significant reduction in brain inflammation on one side of the putamen after 12 weeks of treatment, with 20 of the 30 participants on the drug recording a reduction from baseline. The putamen supports motor control and is affected in Parkinson's disease. Inflammation signals also fell significantly in other regions linked to motor and cognitive function, including parts of the temporal lobe.
A composite score built from motor tasks participants performed on a smartphone moved in the same direction as the clinician assessments, but the difference between groups was not statistically significant. There were also no marked changes in the other parts of the rating scale, or in measures of cognition, quality of life and iRBD symptoms. Syntara said the small study size, the exploratory nature of these assessments and the short treatment period meant the trial was not designed to detect changes across every measure. Further analysis of the digital, clinical, biological and imaging data is still to come.
No treatment-related serious adverse events were reported. All adverse events in both arms of the trial were mild or moderate.
Professor Lewis said the results justified further research. "This study provides convergent exploratory evidence that SNT-4728 has biological activity in people with iRBD, together with an improvement in clinician-assessed motor function that was maintained after treatment ceased. These findings are particularly encouraging because iRBD represents a population at high risk of progression to Parkinson's disease and related synucleinopathies," he said.
"Together with the previously reported TSPO PET imaging findings, these results provide a rationale to evaluate SNT-4728 further in appropriately designed studies, potentially including patients in the early stages of Parkinson's disease."
Syntara chief executive Gary Phillips said the results pointed to a drug that could do more than manage symptoms.
"I'm delighted that the results from this study continue to support SNT-4728's potential benefit for iRBD and Parkinson's patients. There remains a large unmet need for drugs that will go beyond symptomatic control, so the convergence of the biological and clinical outcomes from this study and consequent opportunity to impact disease progression are very encouraging," he said.
Parkinson's Research Ventures, a global program led by Parkinson's UK in partnership with the Parkinson's Foundation, funded the trial. It was run at sites in Sydney and Oxford.
"This study, which we believe is the first interventional study of its kind in iRBD, has been made possible through funding from Parkinson's Research Ventures, the dedication of our Principal Investigators, Professor Simon Lewis in Sydney and Professor Michele Hu in Oxford, the clinical site teams and, most importantly, the participants. We look forward to presenting these findings to the Parkinson's community and to completing the remaining analyses from this important study," Mr Phillips said.
