2020 Fiscal Year Research-status Report
Mapping the Madurella mycetomatis pathogen and host responses during and after antifungal treatment to identify prognostic therapeutic markers for mycetoma
| Project/Area Number |
20K08832
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
アブケセーサ イマド 国立研究開発法人理化学研究所, 生命医科学研究センター, 上級研究員 (10749906)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Mycetoma / Tropical disease / Galleria mellonella / Antifungal |
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| Outline of Annual Research Achievements |
1- In April 2021 we started task 1 (Determine pharmacokinetics) currently we are working on determining pharmacokinetics(PK) and pharmacodynamics (PD) of OSRAVUCONAZOLE (FRCZ) and ITRACONAZOLE (ITZ).We will determine the therapeutic efficacy of FRCZ, via the methodology we have used for ITZ in the past [PMID:28992315]. We will also determine a pharmacokinetic profile for FRCZ in hemolymph over time, as previously described for ITZ [PMID:28992315].
2- We finalized the sample design. Total samples size set to 155.
Total Time points=6 (0hours, 6 hours, 30 hours,54 hours,72 hours,168 hours). Sample type PBS (healthy) (n=30). Itraconazole treated healthy (n=25). Ravuconazole healthy(n=25).PBS infected (n=25). Itraconazole infected(n=25). Ravuconazole infected(n=25).
3- We developed genomic annotation hub database for Galleria Mellonella model and for the pathogen Madurella Mycetomatis. The two annotation hub packages will be released for public FY2021
4- We developed BSgenome data package (Software infrastructure for efficient representation of full genomes) Galleria Mellonella model and for the pathogen Madurella Mycetomatis. The BSgenome packages will be released for public FY2021
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
As many projects and activities, this project was severally impacted by COVID-19 pandemic. The extended lockdown in FY2020 slightly delayed the tasks planned for FY2020 (Labs closed). But we set recovery plan to recover the delayed tasks.
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| Strategy for Future Research Activity |
According to our research plan in FY 2020 we are supposed to perform the following two tasks
Task1 aim to determine the pharmacokinetic profile of Fosravuconazole and Itraconazole. Task2 aim to infect the larvae which include two subtasks. The first subtask to inoculate Galleria mellonella with Madurella mycetomatis fungal pathogen and treat the larvae on 4h 28h and 76h larvae with Fosravuconazole and Itraconazole or solvent and monitor for 10 days to determine the larval survival. Task3 In this task the plan to make research visit to Erasmus University medical center in the Netherlands to discuss about the project implementation and progress. Due to extended lockdown lab closed and we are not able to purchase the Galleria mellonella larvae, the above task delayed. In April 2021 we started task 1 and currently we are working on determining pharmacokinetics and pharmacodynamics of Fosravuconazole and Itraconazole. Task 2 Infect the larvae, This task planned to finish in FY2021. The larvae season will start soon in June 2021, by then we'll be able to purchase the Galleria mellonella larvae and start task2.
The research visit will be schedule after the travel restrictions relax in 2021 or 2022.
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| Causes of Carryover |
Due to the impact of the COVID-19 lockdown, we asked to Incurring FY2020 budget to FY2021. The Incurring will be used as planned in the grant as planned.
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