Introducing Yesterday's Phage Therapy in Today's Medicine

Authors and Disclosures

Jean-Paul Pirnay^*1, Gilbert Verbeken¹, Thomas Rose¹, Serge Jennes², Martin Zizi^3,4, Isabelle Huys^5,6, Rob Lavigne⁷, Maia Merabishvili^1,8,9, Mario Vaneechoutte⁸, Angus Buckling¹⁰ & Daniel De Vos<sup>1

1</sup>Laboratory for Molecular & Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Brussels, Belgium. Laboratory for Molecular & Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Brussels, Belgium
²Burn Wound Centre, Queen Astrid Military Hospital, Brussels, Belgium
³Well Being Department, Queen Astrid Military Hospital, Brussels, Belgium
⁴Department of Physiology, Free University Brussels, Brussels, Belgium
⁵Department of Pharmaceutical & Pharmacological Sciences, Centre for Pharmaceutical Care & Pharmacoeconomics, KU Leuven, Leuven, Belgium
⁶Center for Intellectual Property Rights, KU Leuven, Leuven, Belgium
⁷Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
⁸Laboratory of Bacteriology Research, Faculty of Medicine & Health Sciences, Ghent University, Ghent, Belgium
⁹Eliava Institute of Bacteriophage, Microbiology & Virology, Tibilisi, Georgia
¹⁰Biosciences, University of Exeter, Cornwall Campus, Penryn, UK

Financial & competing interests disclosure
The authors thank the FWO Vlaanderen ('PhageBiotics' research community grant WO.022.09) for its support. J-P Pirnay and M Merabishvili were supported by grant MED 12 of the Royal High Institute for Defence. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

*Author for correspondence
Tel.: +32 2 264 4844 Fax: +32 2 264 4907 jean-paul.pirnay@mil.be

Sidebar

Executive Summary

Spreading Antibiotic Resistance: A Universal Threat

• Overuse and misuse of antibiotics caused the emergence of organisms that are resistant to these medicinal products, leading to increased morbidity and mortality and increased healthcare costs.

• Because new antibiotics have become of limited use and are thus less profitable, pharmaceutical companies are reluctant to invest in the research and development of new antibiotics.

Phage Therapy

• Phage therapy – the use of the viruses of bacteria to fight bacterial infection – was first advocated by Felix d'Herelle in 1919.

• Due to the advent of antibiotics and scientific controversies, phage therapy was abandoned in the western world.

• The current antibiotic resistance crisis has caused a renewed interest in phage therapy.

Phages: Not Your Regular Medicinal Products

• Phages are very different from classical (chemical molecular) medicinal products.

• Phages are natural biological entities that coevolve with and control bacteria in the environment, including humans, which is the basis of sustainable phage therapy.

• There might also be potential negative consequences of bacterial phage coevolution.

Hurdles in the Current Medicinal Product Development & Marketing Model

• When trying to introduce traditional sustainable phage therapy in modern medicine, one is confronted with three issues:

  • The cost of conventional medicinal product development and marketing (millions of Euros) necessitates strong intellectual property protection, but today, for natural phages, this protection is fragile;

  • The time-frames for conventional medicinal product development and marketing (years) are not compatible with a flexible, tailor-made and sustainable phage therapy concept;

  • Responsible and sustainable phage therapy is not compatible with current pharmacoeconomic models.

Current Status

• Only local and sporadic phage applications are performed in the western world, often based on individual approval governed within the 'Declaration of Helsinki' framework.

Conclusion

• Future sustainable phage therapy concepts should fully acknowledge the potential of the coevolutionary aspect of the phage–bacterium couplet.

• More research is needed to determine the potential negative coevolutionary consequences of unlimited phage therapy.

• Our (pharmaceutical) economic models need to be radically reshaped to cater for more sustainable approaches that are beneficial for human survival.