Periodic Reporting for period 1 - MaxImmun (Pharmaco-modulation of epithelia for induction of antimicrobial peptide expression: a disruptive approach to fight antibiotic resistance)
Reporting period: 2024-01-01 to 2024-12-31
Antimicrobial resistance (AMR) is a growing health threat, considered by international bodies to be one of the top global health priorities. In 2019, it was responsible for 1.27 million deaths worldwide. It is estimated that AMR causes 33,000 deaths per year in Europe. Faced with this scourge, the World Health Organization (WHO) has issued an alarming finding: the clinical pipeline for new antimicrobials is dry. The golden age of antibiotics is over, and the development of new and innovative therapeutic strategies to fight infections and reduce spread of AMR is urgently needed. With MaxImmun, we introduce a new concept to fight AMR: the AMP-inducer technology. Based on immuno-stimulatory molecules, this technology aims to selectively boost the expression of the human antimicrobial peptides (AMPs), which are body defenses naturally produced at mucosal surfaces. The novelty of our technology lies in seeking natural molecules that induce a therapeutic expression of our own AMPs, by exploiting the human innate immune system. The technology is introducing a new approach to effectively fight AMR and infectious diseases. Rather than directly targeting a pathogen with exogenous antimicrobials and the risk of resistance development, our technology will promote a natural, endogenous response by leveraging the body’s own defenses. This concept will have the advantage to reduce the selection pressure on bacteria and the risk of promoting resistance. Classical resistance formation by low levels of residual antibiotics will be prevented by our technology, thus providing a sustainable solution against AMR that also will protect from resistance spread among animals and in the environment.
The project activities are ranging from (i) the decryption of the evolutionary processes involved in the potential emergence of bacterial resistance to AMPs, to (ii) the exploration of the marine microbiome and its valuable potential to identify new active molecules with AMP-inducer properties, (iii) the deciphering of molecular mechanisms allowing a therapeutic expression of AMPs by the newly identified active molecules, (iv) the optimization of active molecule efficacy by medicinal chemistry to turn them into drug candidates, and (v) the assessment of the drug candidate efficacy in preclinical models of validation.
The transformative positive impacts of the AMP-inducer technology could be considerable for our society, economy, and environment in several ways. (i) To improve public health, by helping to control the spread of AMR, which could reduce the number of infection-related diseases. More than 1,2 million people worldwide die each year from infections caused by AMR. Products arising from MaxImmun could lower the burden of disease related to these cases. (ii) To reduce healthcare costs associated with AMR infections. According to the WHO, the direct medical costs of treating AMR infections can be up to 20 times higher than the costs of treating infections with antibiotics that are effective. In Europe, AMR costs €1,5 billion per year in healthcare costs and productivity losses. In the long term, the AMP-inducer technology could help to lower these economic losses and to increase productivity and economic growth by helping to reduce work absences related to these infections. (iii) To create a new market and associated jobs for innovative antimicrobials such as AMP inducers, by taking advantage of the “broken” antibiotic market. Our technology will emerge in the current context of the market reform needed to encourage investment and expand the razor-thin pipeline of new antimicrobials in development. With big pharma vacating the space, there are few new antimicrobials currently in the clinical pipeline, most of them being developed by SMEs. (iv) Regarding environmental protection, our technology could help to reduce the amount of antibiotics used, which could reduce pollution, negative impacts on the environment, and help to maintain healthy ecosystems. Classical resistance formation by low levels of residual antibiotics is prevented by the MaxImmun approach. Therefore, the AMP-inducer technology may provide a long-term sustainable solution against AMR, and may also protect from AMR spread in the environment or among animals. (v) To improve quality of life of patients, by stimulating their own defenses for a better health. Beyond the AMR breaking indication, drugs arising from MaxImmun may also be a model that induces a paradigm shift for other diseases: rather than directly targeting a pathology with exogeneous chemicals, the drug elicits a natural endogenous response of the body. This concept of activating the body’s own healing power might be applicable to other diseases. Ultimately, uptake and success of the AMP-inducer technology will depend on how it will be implemented and managed by policy makers, scientists, medical staff and patients.