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Lorenzo Corsini co-founded PhagoMed, a bacteriophage therapy company based in Vienna, Austria, in 2017 and currently serves as CEO with a focus on research and development responsibilities. Lorenzo studied biochemistry at Frankfurt university and holds a PhD from the European Molecular Biology Laboratory (EMBL) in Heidelberg.
What is the biggest question facing your field?
Bacteriophages were first discovered 100 years ago, and soon thereafter used as antimicrobials across the world, to treat cholera, dissentery and other diseases. While they were displaced by small-molecule broad-spectrum antibiotics in Western countries from the ~1940s, they saw continued use in the former Soviet Union. However, well-designed clinical trials have never been conducted these countries. Even worse, the few controlled clinical trials which were conducted in the West, and which were powered to demonstrate efficacy, have failed to do so.
Therefore, it remains unclear if phages can really work in humans, for which indications, and how you would best administer them, at which dose and how frequently. The biggest question in the field is therefore, how can the efficacy of phage therapy be convincingly demonstrated in humans for specific conditions?
Why is it significant?
Phage therapy could be a significant contribution to solving the escalating antimicrobials resistance crisis. Phages are a law of nature, the most abundant biological entity on earth and lyse 50% of the world’s bacterial population every two days. Phages are completely non-toxic, self-replicating and self-limiting. They are also incredibly specific and typically target only a single bacterial species, so that they do not destroy the microbiome – in contrast to small-molecule antibiotics, which inhibit all bacteria, pathogenic and beneficial ones.
Even more importantly, they have a high activity on biofilms, where antibiotics frequently fail independently of genetic resistances. Phages have specific enzymes that degrade the protective extracellular matrix of biofilms, therefore making the bacterial cells accessible to the phages. Phage therapy therefore has the potential to work where antibiotics fail. In a world of escalating resistance, this makes phages hugely significant.
Where is the answer likely to come from?
The answer will come from academia and from biotech startups developing concrete products. Many studies in animals were well designed and have shown efficacy very convincingly. Also in humans, phage therapy has had impressive effects in several applications where they were the only option left, where the patients would have very likely died or faced an amputation without phage therapy. An American professor infected with multiresistant Acinetobacter baumannii was saved with a phage cocktail, and a young woman in Britain was saved from a persistant, life-threatening infection with multiresistant Mycobacterium abscessus.
The lessons from these examples need to be used to understand which indications and under which conditions phage therapy can be effective. Then, clinical trials according to the highest scientific standards need to be conducted, so that many more patients can benefit from this old but still innovative form of therapy.
IMAGE SOURCE: PhagoMed Biopharma GmbH, Anna del Alcazár