Aligning Cures across Neurodegenerative Disease (ACDN)
Funded by the MUR in the frame of the Recovery plan PNRR, ACDN is a multicenter project part of the national center for the development of Gene Therapy and Medicines with RNA Technology (https://www.unipd.it/news/gene-therapy-and-RNA-technology-future-science-padua)
ACDN aims at treating neurodegenerative diseases (NDs) like Alzheimer's Disease (AD), Parkinson’s Disease (PD) and in polyglutamine diseases, including Huntington's disease (HD) and dominant forms of spinocerebellar ataxia (SCA). CESNE will crucially provide large cohorts of patients (cells, biofluids and gastrointestinal tissues) to confirm the preclinical findings, to generate induced pluripotent stem cells to reprogram into neurons and brain organoids in synergy with Nicola Elvassore (Department of Industrial Engineering) and to identify potential disease biomarkers.
ACDN is divided into three, highly interconnected research projects:
1) Gene therapy for polyGlutamine diseases led by Graziano Martello (Department of Biology). This project will delivery, via mRNAs and AAV vectors, gene modifiers suppressing polyQ toxicity that have been recently identified by Martello’s group.
2) Targeting neuroinflammation in NDs led by Paola Pizzo (Department of Biomedical Sciences). As extracellular ATP is a major cause of neuroinflammation in different NDs, this project will deliver specific siRNA (via AAVs or nanocarriers) to target P2X7R purinergic receptors and pannexins-mediated channels responsible for ATP leakage in AD models.
3) Targeting protein aggregation by RNA vaccines led by Angelo Antonini (Department of Neuroscience), Luigi Bubacco (Department of Biology) and Elisa Greggio (Department of Biology). Protein aggregation is a signature of multiple NDs. This project aims at developing an RNA-based vaccine stimulating active immunization against pathological alpha-synuclein in PD.
The gene therapy approaches proposed in the 3 projects will be eventually extended to the other NDs disorders to test their therapeutic potential in a broader setting.
ACDN will benefit from the collaboration of Marisa Brini (Department of Biology) and Tito Calì (Department of Biomedical Sciences) to optimize the delivery strategy and the broader support of the research teams of the National Center for the development of Gene Therapy and Medicines with RNA Technology.
