- Activity 1, project design (Deliverable 1, completed): this activity was intended at the finalization of a detailed study plan describing the experimental activities and steps, the methods, the statistical considerations and data analysis modality that could allow testing in relevant animal models the working hypothesis of the project;
- Activity 2, availability of key resources and material verification (Deliverable 2, completed): this activity was intended at making available all the resources and materials needed to conduct the in vivo POC study;
- Activity 3, set up of the in vivo study (Deliverable 3, completed): this activity consisted in the generation of the study cohorts of the POC of efficacy study; in agreement with the original proposal, we generated two very large experimental cohorts by treating 5XFAD as well as Trem2 ko mice and their corresponding wild type controls. In addition to the planned experimental groups, for assessment of the different variables of interest for clinical development of our treatment approach, intravenous (IV) delivery of the genetically modified cells was also tested. At transplantation, the TI, RI and CI were characterized for cell count and viability, and their in vitro liquid culture progeny by evaluating vector content and clonogenic potential.
- Activity 4, in vivo POC experimental evaluation (Deliverable 4, completed for the 5XFAD cohort, partially completed for the Trem2 ko cohort); the in vivo study was intended to last for a total of 12 months post-transplant in 5XFAD mice and 6 months post-transplant in Trem2-/- KO animals and included the assessment of the feasibility and efficacy of the treatment.
- Activity 5, data analysis and interpretation (Deliverable 5, partially completed); Due to the enlargement of the experimental cohorts as compared to the original plan intended at increasing the informative potential of our study, we have recently completed the work on the 5XFAD model and are still processing some of the activities in the Trem2 ko model. Thus far, data analysis has revealed a superior performance (in the 5XFAD model) of the Reference Item as compared to the Test Item. Completion of the on-going analysis on the Trem2 ko cohorts will allow confirming this finding.
- Activity 6, report generation, patent submission and partnership search (Deliverable 5, partially completed): as stated above, completion of the on-going final testing on the Trem2 ko cohorts will allow us finalizing a report for further IP protection efforts. Meanwhile, we have intensively worked for the establishment of a partnership with ventures and Pharma, established multiple contacts with key stakeholders and are currently awaiting feedback from 2 potential partners. Importantly, based on the work here developed, we successfully applied for an EIC transition grant that is expected to begin on April 1st, 2024.
