The ERC-funded project 233024 (Nuclear Calcium) covered different scientific questions; amongst them, a section was specifically aiming at the investigation of activity-dependent nuclear calcium-regulated gene transcription. We identified a nuclear-calcium dependent target gene that is required both for the maintenance of the length and complexity of dendritic trees: VEGFD (Mauceri et al., Neuron, 2011). The idea of the present ERC-PoC was to investigate the potential of structure-protective activity of VEGFD as a novel therapeutic concept for the treatment of disorders of the nervous system.
We have chosen an in vivo mouse model of stroke (ischemia) for testing our hypothesis and validating our lead compound, VEGFD. In addition, we have generated VEGFD-peptide mimetics (VPMs) and tested them in parallel. We showed that direct brain delivery of full length, recombinant VEGFD (rVEGFD) enhanced functional recovery after stroke in adult mice. We also set-up a novel route of administration to the brain which uses a nose spray and determined conditions for nose-to-brain delivery of both rVEGFD and VPMs. Further, we demonstrated their efficacy in preserving neuronal morphology and reducing brain damage caused by a stroke when delivered intranasally.
A patent application regarding the use of VPMs in neurodegenerative conditions had been filed in 2011. During the course of the ERC-PoC funding period, we received reports from the EU and US patent offices and responded accordingly. In August 2016 the patent was granted by the US patent office. We are currently awaiting the final decision by the EU patent office.
In April 2016, the company 'FundaMental Pharma GmbH' was founded. During second half of the ERC-PoC funding period several Pharma companies and venture capital investors in Europe, US, Japan and Taiwan have been approached to discuss a participation at the financial and operational level. Possible early-stage partners have been identified and discussions have been initiated with qualified personnel to fill key positions once a joint project has been fully implemented and started. The conceptual framework underlying FundaMental Pharma GmbH and the development of the scientific basis for a nose-spray therapeutic for neurodegenerative diseases was honored with the Innovation Price of the German BioRegions.
