Fall Seed Grant Autumn 2024 – Telethon

Towards an in vivo gene therapy for methylmalonic acidemia with homocystinuria type cblC

This project was funded by the Telethon Foundation’s Fall Seed Grant 2024. It aims to develop a mouse model for further study of the disease.

The current lack of a mouse model of the disease limits the development of potentially curative genetic therapies and a better understanding of the mechanisms and biology of the disease. The project aims to generate such a model through genetic techniques, starting from previously available genetically modified mice. Furthermore, genetic engineering tools will be developed, representing the first step towards developing future genetic correction strategies for this disease. Overall, the new mouse model of the disease will improve our understanding of the disease and be crucial for developing new therapeutic approaches, including potential gene therapies.

(Dev Biol. 2020 December 01; 468(1-2): 1–13. doi:10.1016/j.ydbio.2020.09.005.)

Multiomic analysis of the alteration of mitochondrial, autophagic and lysosomal homeostasis in methylmalonic acidemia with homocystinuria type cblC

This project was funded by the Fall Seed Grant 2024 call from the Italian Association of Methylmalonic Acidemia with Homocystinuria (CBLC APS). This project aims to understand the cellular mechanisms underlying development, particularly cellular waste disposal processes, based on the activity of lysosomes and particularly autophagy. Recent studies suggest that these processes may be altered in similar metabolic disorders, contributing to cellular damage. Advanced multiomics techniques will be used to identify and analyze the proteins, metabolites, and lipids involved, in order to describe disease-specific molecular profiles. The goal is to identify potential lysosomal and autophagic dysfunctions contributing to the disease, and to determine whether they are common to different types of methylmalonic acidemia and how they may be linked to other known alterations, such as mitochondrial dysfunction. This is a preliminary study that could lead to the development of new therapeutic strategies capable of improving patients’ quality of life.