TREM2MEDS reports significant progress in advancing the TREM2-HSPC gene therapy approach from TRL 4 toward TRL 5/6, in line with the objectives outlined in the Proposal. As a first step, all key preparatory activities essential for the successful implementation of TREM2MEDS have been completed. This includes activating the working groups both internally (at UNIPD, UNISMART, IMG, and INSERM) and across partner institutions, assignment of tasks, establishment of recurring monthly operational meetings, and drafting of study protocols along with the necessary SOPs. Additionally, all required documentation at due stage has been prepared and submitted for approval by the relevant authorities to obtain authorization for animal testing, ensuring readiness to initiate in vivo experimental activities.
Subsequently, UNIPD has completed Task1.1 – Reduced conditioning regime testing. Briefly, data have been generated to support the use of a novel reduced intensity conditioning regime that allows for a sustained transduced cell engraftment within the myeloid/microglia brain compartment. This regime of low intensity conditioning will thus be exploited in the subsequent tasks. In parallel, INSERM led activities under Task 2.1. Working closely with UNIPD, INSERM has sequenced, annotated, produced and quality-controlled the TREM2_LV lentiviral gene transfer plasmid and implemented a clinically-applicable protocol for the production of the TREM2_LV, with production of research-grade and medium scale preparations. In preparation for Task 2.2 - In vivo biodistribution and safety/toxicology testing, IMG worked closely with UNIPD and INSERM to set up for GLP studies that are planned to commence on M18. To ensure a smooth transition toward clinical translation, a regulatory specialist has been involved in the relevant working groups from the outset of the TREM2MEDS project. This early involvement provides guidance on technical, CMC, and scientific aspects, ensuring that the generated data comply with EMA and FDA regulatory requirements and can be used for IMPD applications. UNIPD has also begun working on the identification of experts to be enrolled in Clinical ADvisory Board activities, in line with the expected timelines.
TREM2MEDS, thus, remains on track, supporting the continued development of the TREM2-HSPC gene therapy in line with the Project Proposal and progressing.
