The Phage Therapy Paradigm: Prêt-à-Porter or Sur-mesure?

Pirnay, Jean‐Paul; Vos, Daniël De; Verbeken, Gilbert; Merabishvili, Maia; Chanishvili, Nina; Vaneechoutte, Mario; Zizi, Martin; Laire, Geert; Lavigne, Rob; Huys, Isabelle; Mooter, Guy Van den; Buckling, Angus; Debarbieux, Laurent; Pouillot, Flavie; Azeredo, Joana; Kutter, Elisabeth; Dublanchet, A.; Górski, Andrzej; Adamia, Revaz

doi:10.1007/s11095-010-0313-5

Cited by 253 publications

(216 citation statements)

References 9 publications

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“…[7][8][9][10][11][12][13] Our response is that work should be done to increase success frequency by using modern molecular biology/biophysics to continuously reoptimize phage cocktail composition and use. We will discuss details, several based on characterization of phage DNA.…”

Section: Phage Therapymentioning

confidence: 99%

“…The Eliava Institute in Georgia, former USSR, 13 has implemented a strategy that includes re-optimizing their phage cocktails to respond to (1) evolution of any given bacterial target, including evolution to drug resistance, and (2) introduction of new bacterial targets. The deliberate changing of cocktails prevents the doing of the usual, clinical tests for effectiveness.…”

Section: Phage Therapymentioning

confidence: 99%

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Enhancing and initiating phage-based therapies

et al. 2014

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D rug development has typically been a primary foundation of strategy for systematic, long-range management of pathogenic cells. However, drug development is limited in speed and flexibility when response is needed to changes in pathogenic cells, especially changes that produce drug-resistance. The high replication speed and high diversity of phages are potentially useful for increasing both response speed and response flexibility when changes occur in either drug resistance or other aspects of pathogenic cells. We present strategy, with some empirical details, for (1) using modern molecular biology and biophysics to access these advantages during the phage therapy of bacterial infections, and (2) initiating use of phage capsid-based drug delivery vehicles (DDVs) with procedures that potentially overcome both drug resistance and other present limitations in the use of DDVs for the therapy of neoplasms. The discussion of phage therapy includes (a) historical considerations, (b) changes that appear to be needed in clinical tests if use of phage therapy is to be expanded, (c) recent work on novel phages and its potential use for expanding the capabilities of phage therapy and (d) an outline for a strategy that encompasses both theory and practice for expanding the applications of phage therapy. The discussion of DDVs starts by reviewing current work on DDVs, including work on both liposomal and viral DDVs. The discussion concludes with some details of the potential use of permeability constrained phage capsids as DDVs.

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Section: Phage Therapymentioning

confidence: 99%

Section: Phage Therapymentioning

confidence: 99%

Enhancing and initiating phage-based therapies

et al. 2014

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“…An analysis of the current European regulatory framework [64] and multiple discussions with experts and the relevant competent authorities revealed that, although the development and marketing of phage medicinal products (including good manufacturing practice production, preclinical and Phase I, II and III clinical trials and centralized marketing authorization) is technically possible, in practice it is not compatible with traditional (sustainable) phage therapy [65].…”

Section: Hurdles In the Current Medicinal Product Development And Markementioning

confidence: 99%

“…IP issues may hamper pharmaceutical companies in the worldwide marketing of generic phage preparations. The long and expensive regulatory pathways form insurmountable obstacles for eventual nonprofit phage therapy centers or SMEs, which opt for a tailor-made concept, and for institutions that would like to use inexpensive phages for commercially unattractive applications (e.g., in developing countries) [65]. GMP: Good manufacturing practice; IP: Intellectual property; SME: Small and medium enterprise.…”

Section: Hurdles In the Current Medicinal Product Development And Markementioning

confidence: 99%

“…A medical doctor is allowed to apply phage therapy where proven therapeutic methods do not exist or have been ineffective (e.g., in MDR infections) and provided that the patient or their legal representative gives informed consent. In France, Alain Dublanchet, a veteran of phage therapy, occasionally applies phages in hopeless osteomyelitis cases [65]. In Australia, phage therapy was recently applied under the umbrella of 'compassionate use' for the successful treatment of refractory P. aeruginosa urinary tract infection in a cancer patient [77].…”

Section: Current Statementioning

confidence: 99%

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Introducing yesterday‘s phage Therapy in today‘s Medicine

et al. 2012

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The worldwide emergence of ‘superbugs’ and a dry antibiotic pipeline threaten modern society with a return to the preantibiotic era. Phages – the viruses of bacteria – could help fight antibiotic-resistant bacteria. Phage therapy was first attempted in 1919 by Felix d’Herelle and was commercially developed in the 1930s before being replaced by antibiotics in most of the western world. The current antibiotic crisis fueled a worldwide renaissance of phage therapy. The inherent potential of phages as natural biological bacterium controllers can only be put to use if the potential of the coevolutionary aspect of the couplet phage–bacterium is fully acknowledged and understood, including potential negative consequences. We must learn from past mistakes and set up credible studies to gather the urgently required data with regard to the efficacy of phage therapy and the evolutionary consequences of its (unlimited) use. Unfortunately, our current pharmaceutical economic model, implying costly and time-consuming medicinal product development and marketing, and requiring strong intellectual property protection, is not compatible with traditional sustainable phage therapy. A specific framework with realistic production and documentation requirements, which allows a timely (rapid) supply of safe, tailor-made, natural bacteriophages to patients, should be developed. Ultimately, economic models should be radically reshaped to cater for more sustainable approaches such as phage therapy. This is one of the biggest challenges faced by modern medicine and society as a whole.

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