For the first objective, we have set up protocols for the production of GMP-grade modified peptides. Efforts are currently focused on preparing non-GMP exendin-700DX photosensitizer variants for toxicity studies, preclinical validation, and future GMP production. Work to achieve the second objective is still ongoing, but significant progress has been made. We have implemented in vitro and ex vivo models and techniques to investigate the biological effect of tPDT and optimize the pharmacological and light dose. This will be investigated in more depth in vitro and in vivo in rat models. In addition, we are planning an in vivo study in rats to determine the dosimetric protocols when using radiolabeled EX as a companion diagnostic. Altogether, these findings will ultimately be translated to individually tailored PDT in human use (WP4/5).
The work of objective 3 is still ongoing. The biological effect of exendin tPDT is being investigated in relevant in vitro and ex vivo models These results will lead to tailored protocols for the in human proof-of-concept, and validation of these results will be done. Work on objective 4 has not been started yet as we need to await for the preclinical development in the other workpackages (WP2 and 3). However, contacts within the participating sites with supporting departments necessary for successful execution have been made. Furthermore, microscope analyses have been started as preparation in WP5.
Objective 5: there has been a significant investment in ensuring that the HI Global Registry (HIGR) can serve as the go-to international open-access registry for CHI research and data collection. Significant progress has been made to increase the quality and amount of data available in HIGR and to ensure that it is readily available to researchers interested in utilizing the data. In addition, ethics approval has been obtained for measuring quality of life and burden of disease in CHI. Patient and healthcare professional recruitment is currently ongoing and proceeding. The qualitative data collection is currently ongoing. Concurrently, the qualitative data analysis has been initiated. The initial transcripts are currently undergoing coding and thematic analysis as part of an iterative process.
Objective 6 is not fully achieved since it is still ongoing. We have contacted an international organisation to seek advice from experts in the field of pediatrics. They will provide input on the setup of toxicity studies and the related documentation required for EMA submission and subsequent phase II and III trials. We plan to include them in the LightCure consortium.
Significant progress have been achieved for objective 7. We actively launched glucose as a vital sign to raise awareness, to encourage early diagnosis and effective management of HI to reduce brain damage. We engaged in activities targeted at medical professionals and the public, including an international CHI awareness day, the CHI documentary film, participation at medical conferences, and began planning and drafting the letter-writing campaign for hospitals. We also created long-form and short form advocacy statements and a list of essentials for people with HI that are posted in 5 languages on our website. We upgraded and expanded materials targeted to CHI families for education and support. For objective 8, a patient advisory board is established and actively engaged in activities for exploitation and dissemination as well as attended in-person consortium meetings to provide feedback on the on-going advocacy and scientific aspects of the project.
Work is still ongoing for objective 9, but the final proposal for the laboratory testing is completed and will be reviewed soon by the medical ethical committee.
