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Assessing the Ability of Dapansutrile, a Selective, Oral Inhibitor of the NLRP3 Neuroinflammatory Pathway, to Mitigate Progression of Parkinson’s Disease

Study Rationale: Increasing scientific data indicate the role of neuroinflammation in the pathology of Parkinson’s disease (PD) and related alpha-synucleinopathies. Dapansutrile (lab code: OLT1177®, Olatec Therapeutics LLC) is a small molecule and a selective inhibitor of a neuroinflammatory pathway known as NLRP3. Taken orally, the drug crosses the blood-brain barrier and modulates neuroinflammation. Initial studies in preclinical mouse models show that dapansutrile reduces the levels of alpha-synuclein aggregates, suggesting that the drug could be beneficial for treating PD.

Hypothesis: We hypothesize that by targeting neuroinflammation, dapansutrile will protect dopamine-producing neurons, ameliorate alpha-synuclein pathology and stop the progression of motor symptoms in PD and related alpha-synucleinopathies.

Study Design: In this study, we propose to test dapansutrile in an alpha-synuclein propagation model and in a transgenic alpha-synuclein mouse model. These models will allow us to study the effect of dapansutrile on motor deficits, the clearance of alpha-synuclein, neuroinflammatory signaling and the loss of dopamine-producing neurons. Dapansutrile will be delivered orally via enriched food pellets (provided ad libitum). PK will be performed to confirm exposure levels. 

Impact on Diagnosis/Treatment of Parkinson’s disease: By confirming dapansutrile’s ability to treat neuroinflammation in preclinical models of PD, this project will pave the way for a prospective human proof-of-concept clinical trial in PD and other CNS disorders.

Next Steps for Development: Because the long-term safety of dapansutrile has already been demonstrated in animals, a Phase 2 clinical trial in people with PD and related alpha-synucleinopathies could start as soon as practical following successful completion of the proposed preclinical studies.


  • Nadia Stefanova, MD, PhD

    Innsbruck Austria

  • Charles A. Dinarello, MD

    Denver, CO United States

  • Jesus Amo-Aparicio, PhD

    Denver, CO United States

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