After the PANA full project implementation, several achievements have been reached in several fields such as the following:
• The development of high-affinity antibodies against p-Tau and ac-Tau.
• Epitote characterization and sequencing of novel (p-Tau) and (ac-tau) monoclonal antibodies with potential diagnostic and therapeutic propierties.
• GMP manufacturing plan of (p-Tau) monoclonal antibody.
• the development of reliable, stable and safe radiolabelled nanoconjugates that can be used as potential 1) novel contrast agents in MRI/PET and 2) innovative carriers for therapeutic compounds.
• novel in-vitro diagnostics methods (ELISAs) for specific tau isoforms (p-Tau and ac-Tau).
• Novel immunotherapy against phosphorylated Tau without toxic effects.
The development of potential patent applications to secure IP protection and/or future explotation actions for the custom-made antibodies have ben performed. rThe PANA consortium is committed to achieve further exploitation of the project results beyond the project implementation and will therefore continue to pay high efforts to the IP protection and further exploitation of the results. In addition to the IP work, a comprenhensive approach have been carried-out in order to gain in-depth knowledge of AD and in the specific Tau-based approached for in-vitro and in-vivo diagnosis, as well and in the filed of immunotherapy. Main competitors and compounds under development have been identified. The findings of this analysis have decisively contributed to help SERGAS to found a start-up that will exploit its own results. This company, named Lincbiotech SL.
Although it is not completely understood the contribution of genetics and environment to AD, current data suggests that AD is a continuum of several genetic and environmental factors where misfolding and aggregation of certain proteins such as tau. Tau phosphorylation have been related to reduced microtubule affinity and increased aggregation of tau. On the other hand, more recent findings have confirmed relevant roles of acetylations in tau microtubule assembly, degradation and aggregation. The products are expected to be formulated as solutions for injection or infusion. The dose level has not been determined. The posology is suspected to require multiple administrations at defined intervals. The route of administration is to be defined. The PANA consortium presented a regulatory roadmap for the development of E11 and B6 as a new therapy for the treatment of early AD.
Summarizing all the work carried out so far, PANA consortium has been able to provide solid proof-of-concept for the following PANA products:
• An innovative in-vitro system, based on tau oligomers, PANA001: Kits ELISA for detection of misfolded Tau in CSF were optimized and were clinically validated (in comparison to current gold-standards) showing promising results that have to be validated in further multicentric and larger clinical studies.
• A dual theragnostic contrast agents PANA002: Proof-of-concept for novel contrast agent based on both p-Tau mAb (89Zr, 125I ) and nanoconjugates (89Zr, 125I ) have been already tested in-vivo. Positive results in terms of signal were found, and biodistribution analysis was carried out. However, a remaining issue to be overcome is the limitated uptake of the brain. The consortium worked on different strategies to optimize these results, but unfortunately, no positive results were obtained. Novel developments focused on BBB cross are needed.
• –PANA003- a novel immunotherapy against tau aggregation proof-of-concept study to assess safety and efficacy was carried out showing promising data.
