IRET Foundation is the lead partner of the N2ERT project, which started on 06/02/2024 and will run for 30 months.
N2ERT will develop a prototype technological platform to optimise Nanomedicine for the delivery of therapeutic enzymes to the brain, to improve neurological symptoms in rare lysosomal storage disorders. The platform will accelerate the TRL4 to TRL6 transition, according to regulatory agency specifications. The nanoformulation will protect the enzymes’ biological activity and direct its delivery to the brain; it will be tested for the rescue of the biological functions in cellular and animal models of disease. The platform’s development will be accompanied by GLP toxicity testing and will include GMP industrial scalability testing in an industrial environment. N2ERT will nanoformulate the enzymes alpha-mannosidase (human recombinant form, velmanase alpha) and sphingomyelinase (human recombinant form, olipudase alpha-rpcp) supplied by Chiesi Farmaceutici, to create nanomedicines with FDA/EMA approved materials for human use. Cell systems based on primary cells derived from patients and transgenic mice carrying the human mutation will be used to study efficacy and safety in the GLP environment (TMR company).
Objectives and expected results
N2ERT aims to bridge the gap between the production of therapeutic systems and their biological validation, with an integrated platform for prototype production, evaluation and validation of advanced nanomedicines for therapeutic protein replacement. It will employ recombinant human therapeutic enzymes (aMAN alpha-mannosidase and AM acid sphingomyelinase) used for the treatment of rare neurometabolic lysosomal storage diseases. N2ERT has the following technological objectives:
O1. Development of 2 NMed to protect the biological activity of the enzyme (nERT-aMAN and nERT-ASM);
O2. Development of at least 1 NMed designed for delivery across the blood-brain barrier (BBBnERT);
O3. Ability to deliver an effective dose (up to 10% of the injected dose) of enzymes into the CNS;
O4. Consolidation of rapid, accurate, efficient and robust ‘high throughput’ in vitro safety tests for rare lysosomal storage diseases;
O5. Identification and validation of efficacy readout assays by rescuing the enzymatic activities of nERT-aMAN and nERT-ASM in vitro and in vivo. The intermediate advancement (TRL5) is the optimised platform for key factors in the design, production, evaluation and validation of NMed designed for the enzymes of interest, for safety and biological efficacy assays in the GLP environment. TRL6 will be reached at the end of the project through validation in the GLP/GMP environment.
The partnership brings together laboratories of the High Technology Network (IRET Foundation, CIRI SdV - University of Bologna, CIDSTEM - University of Modena and Reggio Emilia) and companies (Chiesi Farmaceutici Spa, Transmed Research Srl), leaders in their respective fields, which represent a good guarantee of achieving the project objectives.
The N2ERT project is co-funded by the ERDF RP 2021-2027, ACTION 1.1.2 of the Emilia-Romagna Region, for a total project cost of 694,632.43€ (contribution of 499,232.71€).
