Periodic Reporting for period 2 - INPACT (Innovative peptides against cancer and pathogenic bacteria, with advances in science, biopharmaceutical drug development, product market targeting, training , and communication.)
Reporting period: 2017-02-01 to 2019-01-31
The major outcome intended for the project is to develop new drug leads to target both infectious diseases and cancers. Specifically, the new drugs will combine the ability to kill bacteria and tumour cells with capability to translocate the blood-brain barrier; therefore, these innovative drugs will be capable of targeting brain tumors and brain-hidden pathogens.
1. Scientific knowledge
INPACT has contributed to the publication of more than 20 research papers focused on anti-bacterial and anti-cancer drug leads. New chemical entities were found and characterized. Moreover, the technologies and methodologies that the consortium developed to make these drugs traverse the blood-brain barrier are an important asset for other applications for which brain-targeting is essential.
2. Training of improvement of career prospects
INPACT has enabled advanced training to young researchers and early career stage professionals in international environments, most of the times in a different sector of activity. This investment has had a direct impact in the recruitment of fellows for first job contractual recruitment or improvement of career prospects for untenured early stage academic researchers.
3. Translation of scientific knowledge to economy
INPACT generated technology to bring anti-microbial and anti-cancer drugs across the blood-brain barrier. This technology was patented under agreement between academic partners of INPACT and Technophage SA, a non-academic partner of INPACT. In addition to the technology itself, an application based on targeting engineered antibodies to the brain was also patented.
A third patent is being prepared for submission. This patent is based on the use of an antimicrobial drug lead used in INPACT to abrogate infections of a viral pathogen.
4. Science Communication
Throughout the 48 months of activity the INPACT team has been very active on science communication. The training of a young fellow at the media partner resulted in several outreach papers in the specialized magazine Ciência Hoje (“Science Today”), for instance. The participation of INPACT fellows in the European Researchers’ Night is also deemed important. Collaboration with the media in TV shows, newspapers, and broad scope magazines are also worth highlighting, as well as seminars and conferences for teenagers and children in schools.
5. A sustainable and enduring collaborative network
The results obtained with INPACT enabled a successful application to funding to perform follow up studies from the European Innovation Council, under the FET-OPEN program. Three partners members of INPACT constitute the winning consortium. This follow up is deemed important because it demonstrates that the scientific outcomes of INPACT are high quality and high impact, and the influence of INPACT extends far beyond the time period of the project itself.
1. We have identified and characterized two peptide shuttles to reversibly cross the blood brain barrier. After proof of concept studies, these peptides were patented are now being developed to deliver anti infective, anti cancer, and biological drugs to the brain.
2. Viral proteins have important, albeit underexplored, anti bacterial and anti cancer domains. We have systematically mined viral proteins and found drug leads based on the sequences of some of these domains using bioinformatics tools.
3. Recently we have succeeded in finding and characterizing the mode of action of a very active anti bacterial biofilm drug lead. This drug kills bacteria in preformed biofilms without remains of persistent survival of cells. Moreover, we have followed quantitatively the diffusion of the antibiotic through the biofilms and recorded, also quantitatively, the kinetics of killing through the biofilm as the antibiotic diffuses.
4. In an entirely original approach to prevent breast cancer brain metastases, we have found that a protein present in common bean, the defensing PvD1, is able to kill primary cancer cells and abrogate their adhesion to the blood-brain barrier. This dual action is extremely important as it addresses two major unmet needs (primary tumor and metastatic spreading) with a single drug.
5. INPACT enabled writing of a new textbook with an innovative pedagogical approach to training in medical biochemistry, with world-wide distribution. This outcome will be important in the training of future scientists and health care practitioners, taking the legacy of INPACT far beyond the period of the project itself.
Video presenting INPACT:
Video explaining the anti cancer activity of PvD1, a bean protein: