The Clogged Antibiotic Pipeline Challenges and Tricky Targets in Drug Development
Phd Student: Laura Daniela Martinenghi
Email: laura.martinenghi@sund.ku.dk
Relevant link: https://ucph-ku.zoom.us/j/69242001796?pwd=XaTg8twZf5YNxG46ajl3vtXPYIR3lN.1
THE PROJECT
Antimicrobial Resistance (AMR), often called a "silent pandemic," poses a serious threat to global health as bacteria and other pathogens grow increasingly resistant to existing antibiotics. This resistance is fueled by not only biological factors but also by insufficient healthcare access, outdated testing methods, restrictive regulations, and limited funding for research. Over the past few decades, only 68 new antibiotics have come to market, and the pipeline for new treatments is alarmingly sparse, with only a handful of truly novel antibiotics in development.
This research examines the complexities within the antibiotic development pipeline, challenging the belief that all easy discoveries have already been made. Part of the DryAp project, a collaborative European effort, the thesis argues that the pipeline isn’t “empty” but rather “clogged” with promising compounds that remain undeveloped due to regulatory, financial, and scientific obstacles.
The thesis includes case studies on synthetic antibiotics, historical analyses of bacteriocins (natural bacterial compounds), and innovative methods like a new cell culture screening approach. Additionally, it explores the repurposing of old drugs and innovative delivery methods for better effectiveness. This work emphasizes the need for a patient-centered approach in AMR research, highlighting how historical challenges and recent innovations must inform future efforts. The ultimate goal is a shift in drug development that prioritizes effective, accessible treatments to tackle AMR and ensure global health security.
THE PURPOSE
The purpose of this thesis is to challenge the notion that the antibiotic development pipeline is empty, proposing instead that it is "clogged" with promising compounds hindered by economic, regulatory, and scientific barriers. The research aims to reveal the underlying complexities and paradoxes in the antibiotic discovery process, advocating for a more patient-centered approach to address the growing issue of Antimicrobial Resistance (AMR). By examining historical cases, innovative methods, and collaborations like the DryAp project, the thesis seeks to inspire renewed commitment and practical strategies to unblock the pipeline, leading to more effective and accessible treatments to combat AMR.
THE RESULTS
Witness Seminar on Plectasin (Nov 16, 2023):
Highlighted broader challenges in the antimicrobial pipeline.
Emphasized the need for cross-stakeholder collaboration.
Produced 4 publications, 2 drafts.
- Bacteriocins as a possible candidates and an historical overview.
- Paradoxes of the antimicrobial research
- Peptides history : Plectasin
Identified 6 antimicrobial candidates:
2 dendrimer-ciprofloxacin conjugates effective for Gram-positive and -negative, targeting respiratory disease.
4 repurposed phenothiazine drugs targeting Gram-positive bacteria.