Periodic Reporting for period 5 - FAIR-PARK-II (Conservative iron chelation as a disease-modifying strategy in Parkinson’s disease: a multicentric, parallel-group, placebo-controlled, randomized clinical trial of deferiprone)
Reporting period: 2021-05-01 to 2021-10-31
In WP, submissions to competent Authorities and Ethical committees have been done. Drug was managed by ApoPharma. The study has been monitored. During the 5th period, the database has been cleaned, and locked on 17/09/21. The statistical analysis of the project is still under progress. In WP3, the sponsor selected 24 European expert centres, to perform patients’ recruitment. On December 2019, 372 patients were included.
In WP4. The MRI and Dat scan protocols were successfully implemented. The protocol of Transcranial Ultrasound was active. A secure digital tool for data sharing and imaging services was finalized. In the sub-task 4.3 data analysis is ongoing. Biologic samples of the subtasks 4.4 4.5 and 4.6 were delivered to responsible working groups, underwent quality control and are awaiting analysis for pre-defined parameters.
WP5 provided a health economic evaluation to evaluate the resource use, costs and health status in order to calculate the cost-effectiveness of the treatment. The SENSE-PARK wearable device system measured in daily life over the entire day. Raw data were then extracted and transferred in a data format ready to run analysis and algorithm applications WP6, FPII logo, graphic standard, brochures, flyers and public website were created. The protocol was registered on the ClinicalTrials.gov and Fox Trial Finder Publication Policy and dissemination strategy were made and the exploitation plan updated in 2017. The consortium participated in major events to present the project and disseminate results. In WP7, the setup of the study was compliant with all ethical aspects.
B- Impact of DFP treatment on the autonomy, quality of life and health economics: We were not able to demonstrate an improvement for these aspects. To hope for a therapeutic effect on quality of life and autonomy, it will be necessary to conduct a therapeutic trial in patients receiving a dopaminergic treatment and to carry out a therapeutic trial of more than one year.
C- To make iron chelators available to PD patients more rapidly: Development in PD will be successful if DFP is co-prescribed with dopaminergic therapy and evaluated over a longer term to demonstrate clinical impact. We hope to convince Chiesi and other laboratories to carry out this development.
D- Surrogate biomarkers and theranostic biomarkers: We want to develop surrogate biomarkers by analysing a large range of biological, radiological and genetic biomarkers. An analysis of theranostic biomarkers could help the choice of treatment after only few months. Several biomarkers could change the clinical management of PD and facilitate assessment of the risk/benefit balance for treatment decisions.
E- European clinical networks for ND: We obtained another European grant (Center of Excellence in ND: COEN “Iron-Syn”) to better decipher the regulated cell death associated with iron accumulation and the alpha synucleinopathy. We develop a new iron chelator (SP420 from Abfero pharmaceuticals/Pharmacosmos) for conservative iron chelation as a disease modifying modality in PD, thanks to another European funds (EUROSTAR: PD-IRON SYN)
The expected impacts:
- Iron chelation is the leading treatment for ferroptosis, a new form of regulated iron-related death. However, many other anti-ferroptosis treatments are in development, such as the one with our partner PTC therapeutics.
- FPII study has been a catalyst for preclinical research, particularly in demonstrating the importance of iron-related regulated death: ferroptosis. It has also been a catalyst for pharmaceutical development of new iron chelators and new anti-ferroptotics. The study also catalyzed the search for combination biomarkers to demonstrate neuroprotection that look promising to support future therapeutic trials. Finally, FP II provided clinical evidence that dynamic iron accumulation in the nigro-striatal pathway is a mechanism for compensating for dopamine depletion by increasing endogenous dopamine synthesis. However, we suspect that this accumulation is to the detriment of neuronal survival by promoting ferroptosis and precipitating the aggravation of the disease. Therefore, the strategic hypothesis is to treat patients with a moderate dose of iron chelator combined with dopaminergic therapy to avoid symptomatic worsening and allow neuroprotection.