Olatec Therapeutics, a clinical-stage biotechnology company focused on developing selective NLRP3 inflammasome inhibitors, has presented new preclinical data supporting its lead candidate dapansutrile at The Michael J. Fox Foundation (MJFF) Parkinson’s Disease Research Exchange forum.

The studies were funded by MJFF for Parkinson’s Research and conducted by Dr. Nadia Stefanova at the Medical University of Innsbruck. The findings demonstrated that chronic oral administration of dapansutrile produced broad, durable, and clinically relevant disease-modifying effects in two translational mouse models of Parkinson’s Disease (PD).

In the six-month preclinical studies, dapansutrile was administered orally at a well-tolerated, human-equivalent dose. Treatment resulted in significant inhibition of neuroinflammation, including reduced microglial and astroglial activation, while preventing or markedly improving motor deficits. The therapy also protected dopaminergic neurons in the substantia nigra and striatum and reduced α-synuclein pathology and intracellular accumulation.

Dr. Stefanova, stated, “We are excited that our results provide a strong translational rationale for the clinical development of dapansutrile in Parkinson’s disease and related disorders. Beyond efficacy in mouse models, these findings establish a direct mechanistic link between dapansutrile and the pathogenic microglial profile associated with Parkinson’s disease.”

Damaris Skouras, Co-Founder and Chief Executive Officer of Olatec Therapeutics, added, “We are grateful to MJFF and Dr. Stefanova for supporting these studies, which deliver compelling mechanistic and biomarker evidence that dapansutrile can modify core neurodegenerative processes in Parkinson’s disease models.”

Notably, dapansutrile reversed pathogenic microglial gene-expression signatures, normalising approximately 75 percent of upregulated genes, including Lrrk2, and counteracting disease-associated microglial phenotypes identified through human single-cell RNA sequencing. The treatment also lowered plasma levels of Neurofilament light (NfL) and interleukin-18 (IL-18), biomarkers that showed strong correlation with improvements in motor function.

These therapeutic effects and target engagement evidenced by reduced levels of NLRP3, ASC, cleaved caspase-1, IL-1β and IL-18 in the brain were confirmed in both a Parkinson’s disease prevention model using α-synuclein pre-formed fibrils and a therapeutic model initiated after symptom onset using PLP-α-synuclein transgenic mice.

The newly presented data further strengthen the translational foundation for dapansutrile’s upcoming Phase II clinical trial, which is expected to begin enrolling patients soon at the University of Cambridge. If the findings are confirmed in patients treated for 12 months, dapansutrile could become the first oral disease-modifying therapy targeting NLRP3-driven neuroinflammation in Parkinson’s disease.