P3.10. ESTIMATION OF THE THERAPEUTIC POTENTIAL OF THE ANTI-INFLAMMATORY DRUGS IN THE TREATMENT OF PARKINSON'S DISEASE
Agnieszka Zelek-Molik1, Anna Alwani1, Adam Roman1, Adam Bielawski1, Tomasz Lenda2, Piotr Chmielarz1, Jolanta Konieczny1, Grzegorz Kreiner1
1 Maj Institute of Pharmacology Polish Academy of Sciences, Department of Brain Biochemistry, Smętna 12 St, Kraków, Poland
2 Maj Institute of Pharmacology Polish Academy of Sciences, Cephares, Smętna 12 St, Kraków, Poland
INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, with a key role of α-synuclein aggregation and neuroinflammation. Epidemiological observations and preclinical studies suggest that use of anti-inflammatory drugs (mainly non-steroidal anti-inflammatory drugs, NSAIDs) protect against PD. Unfortunately, the long term usage of NSAID causes numerous gastrointestinal side effects and is cardiotoxic. Preclinically data on NSAIDs in PD is limited to older, acute neurotoxic models, while rationale favors their use in prodromal PD stages – and conversely – in novel, progressive PD models like TIF1ADATCreERT2 genetic model, and the preformed α-synuclein fibril (PFF) injection model.
AIM(S): The study aimed to select a candidate among the available and developing anti-inflammatory drugs that could be investigated in such models.
METHOD(S): We searched the literature using the PubMed database for pharmacotherapeutic strategies for neuroinflammation in neurological diseases, focusing on their blood-brain barrier (BBB) permeability and the safety of their long-term use.
RESULTS: Publications have shown that the most popular strategies for treating neuroinflammation are still the inhibition of enzymes of various types of cyclooxygenases. Our attention was drawn to the compound MIP001, which showed therapeutic efficacy in animal models of inflammation and pain. In addition, the MIP001 showed no ulcerogenic effect and no other undesirable effects on the gastrointestinal tract. Despite the lack of studies on the penetration of BBB, MIP001 reduced locomotor activity, prolonged sleep time after hexobarbital, caused headaches and dizziness in pre- or clinical studies.
CONCLUSIONS: Because the higher safety after the long-term use of MIP001 and data suggesting its BBB penetration, MIP001 seems to be suitable candidate for further studies of its therapeutic potential in animal models of PD.
FINANCIAL SUPPORT: The study was supported by a programme coordinated by the Medical Research Agency, co-financed by the European Union under the NextGeneration EU initiative, within the framework of the National Recovery Plan, Component D, Investment D3.1.1 (project no. 2024/ABM/03/KPO/KPOD.07.07-IW.07-0173/24-00)