We have engineered a synthetic protein, BLINK2, with potential application as an innovative therapeutic tool in pain.
The main goals of the PoC project BREAK were to:
1- further improve BLINK2 properties in the lab by means of synthetic biology approaches
2- test its analgesic effect in vivo in animal models in the central nervous system (CNS)
3- test its analgesic effect in vivo in animal models in the peripheral nervous system (PNS)
4- identify the best root of exploitation by the medical industry
Goal 1. We have successfully isolated a new channel variant, BLINK3, with higher expression level in mammalian cells.
Goal 2. BLINK expression in CNS has shown that it is delivered to the presynaptic compartment where it decreases release probability of the presynaptic terminal upon light activation, suggesting that BLINK can be suited for terminal, and not only somatic, inhibition. Moreover, behavioral experiments in vivo, in an open field arena, promoted self-grooming, showing that BLINK2 activation mediated behavioral effects.
Goal 3. In vivo expression of K+ channels in animal pain models has been attempted twice during the project but was heavily delayed by the outbreak of the Coronavirus pandemia. Although we have established collaboration in Italy first and international collaboration later, our plan to perform the experiments in animal pain model could not be carry out, notwithstanding the programmed visit of one member of our team to the collaborator lab at the University of Arizona, Tucson. Nonetheless we were able to implement a back up plan to perform the main experiment, expression of BLINK2 in dorsal root ganglion (DRG) through a local collaboration, at the University of Milano. After an initial delay due to the need to set up an adequate protocol to transfect the DRG, we are presently performing the control experiments and we will evaluate soon the effect of BLINK2 activation in DRG inhibiting DRG firing.
Goal 4. Alongside the technical activities, the team carried out a series of activities aimed at identifying the best route to exploitation. The objective was mainly to decide on the future path, finding possible applications, partners, defining the opportunity to create a start-up and identifying sources of funding, all to be gathered in a business plan. The activity started by interacting with some key stakeholders in the field of pain therapy and pharmaceutical industry. Moreover, the team interacted with different companies: for preclinical tests, for clinical protocol definition, regulatory advice and for strategy and business support.
A patent application (Italian PA (102021000023987), 2021) has been submitted to protect the core of the BREAK technology. This is a key asset for future exploitation. From the preliminary FTO analysis carried out, there appear to be no current limitations to future commercialization.
One of the open questions of the project was the opportunity to create a start-up. Setting up a start-up could definitely facilitate the sponsorship of pre-clinical and clinical trial activities, which are essential both to receive funding from private investors and if the team wanted to license the technology. From the interactions we have had, it seems unlikely to raise the attention of pharmaceutical companies and investors before completing at least phase 1-2 clinical trials. Thus, the team intends to spin-off from the University creating a new group of young and skilled people with industrial attitude.
The CRO JSB Solutions carried out a regulatory study in order to classify the technology behind NIRWANA. The result of the study is that the system should be classified as a "Gene therapy medicinal product", following the regulations
Through interaction with stakeholders, the team identified a number of partners with whom the strategies defined by the business plan were outlined and it is presently discussing the possibility to establish a start up company to exploit the patent.
