Targeted Nose-to-brain Treatment of Neurometabolic Diseases with RNA Nanomedicines – NtB-4NeuroMed

Funder: Project funded under the National Recovery and Resilience Plan (PNRR), Mission 4 Component 2 Investment 1.4 – Cascade Call related to the Program “National Center for Gene Therapy and Drugs based on RNA Technology (CN RNA & GENE THERAPY)” funded by the European Union – NextGenerationEU;

Award Number: Cascade Call related to the Program “National Center for Gene Therapy and Drugs based on RNA Technology (CN RNA & Gene Therapy)” CN00000041, CUP E93C22001080001;

Start date: 01/08/2024

End date: 31/07/2025

Total NRRP funding for the cascade call: € 2.600.000,00

Total NRRP funding for Unipr: € 208.660,00

The NtB-4NeuroMed project aims to develop lipid nanoparticles (LPNs) for targeted nose-to-brain delivery of RNA therapeutics, specifically for treating the rare neurometabolic Lafora disease. The project, led by the University of Parma, combines expertise in medicinal chemistry, nanotechnology and nano-bio interactions to create RNA-loaded LPNs modified with lipopeptides targeting ACE2 receptors on olfactory neurons. This innovative approach aims to provide a non-invasive method to deliver RNA therapeutics directly to the brain, bypassing the blood-brain barrier and improving the efficacy of treatment for neurological disorders.

 The project includes lipopeptide synthesis, production and characterization of LPNs, and evaluation of their performance in vitro and ex vivo. The goal is to design LPNs with specific properties that enable mucopenetration, olfactory neuron targeting, and efficient enzyme expression. By exploiting the nose-to-brain route, the project aims to develop a platform that can be used for various RNA-based therapies, potentially extending beyond Lafora disease to other central nervous system disorders.

The University of Parma is involved in all the Project's Work Packages (WP):

• WP1: Lipopeptide synthesis (Activity 1)
• WP2: Lipid nanoparticles manufacturing (Activity 2)
• WP3: Nanomaterial-biological interactions studies (Activity 3)

• Department of Food and Drug

• Università degli studi di Modena e Reggio Emilia

The NtB-4NeuroMed project aims to provide proof-of-concept for RNA-loaded non-liposomal LPNs that can effectively target olfactory neurons and deliver therapeutic RNA to the brain. This will include lipopeptide synthesis and optimization, successful production and characterization of LPNs, and validation of their targeting and delivery capabilities in relevant biological models. The project aims to provide a new drug delivery platform that can improve the precision and efficacy of RNA-based therapies for central nervous system diseases.

 In addition, the project aims to contribute to the broader field of RNA therapeutics by addressing the challenges of non-invasive delivery and organ-specific targeting. Successful development of this platform could pave the way for new treatments for rare genetic diseases and other neurological disorders, ultimately improving patient outcomes and advancing the field of personalized medicine. The results of the project will also be disseminated through scientific publications and collaborations, further increasing the impact of this innovative research.

National Center for Gene Therapy and Drugs based on RNA Technology