2023 American Academy of Neurology Abstract Website

Giulia D'Urso¹, Alessandra Thomann¹, Judith Anzures-Cabrera², Bastian Zinnhardt¹, Benedicte Ricci¹, Lorna Bailey³, Krzysztof Smigorski¹, Venissa Machado¹, Eva Zsuszsanna Mracskó¹, Nicola Pavese⁴, Kenneth Marek⁵, Kathrin Brockmann⁶, Tanya Simuni⁷, Nicoletta Milani Muelhardt¹, Gennaro Pagano¹
¹Roche Pharma Research and Early Development (pRED), F. Hoffmann - La Roche Ltd, ²Roche Products Ltd, ³Product Development Safety, F. Hoffmann-La Roche Ltd, ⁴Newcastle University, ⁵Invicro, A Konica Minolta Company, ⁶University Hospital Tuebingen, ⁷Neurology, Northwestern University Feinberg School of Medicien

Objective:

Here we describe the study design of a Phase Ib study to test the safety, pharmacokinetics and pharmacodynamics of selnoflast, a novel NLRP3 inflammasome inhibitor, in individuals with early-stage PD.

Background:

Release of pathological alpha-synuclein from damaged neurons may contribute to dopaminergic neuronal loss in Parkinson’s disease (PD) through microglial response upon activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. We hypothesise that blocking the NLRP3 inflammasome with selnoflast (RO7486967) may reduce brain and cerebrospinal fluid (CSF) inflammasome levels and microglia activation, thereby reducing the rate of neurodegeneration in PD and potentially reducing the rate of PD progression.

Design/Methods:

A total of 48–72 individuals with early-stage PD (treatment naïve or on stable symptomatic therapy) will be recruited in this Phase Ib study to test the safety, pharmacokinetics and pharmacodynamics of selnoflast, a novel NLRP3 inflammasome inhibitor, in early-stage PD.

Results:

The study design will be described, including inclusion/exclusion criteria, safety, pharmacokinetics and pharmacodynamic parameters (CSF and positron emission tomography imaging) selected for this Phase Ib study.

Conclusions:

To characterise a novel compound acting on the inflammasome, an innovative Phase Ib study design is needed to investigate safety, pharmacokinetics and pharmacodynamics.