Dr James Duboff
Strategic Partnerships Director, Genomics England
New antibiotics cannot be widely prescribed without encouraging resistance to arise, posing a major challenge in how to address the R&D costs associated with novel drug development.
When a pharmaceutical company develops a new improved drug, it will typically outcompete existing products and be sold to as many patients as possible. This enables patients to benefit from the upgraded therapy and the company to recoup their R&D costs.
The challenge of new antibiotics
In the case of a new antibiotic, the opposite is true: the drug is actively held back from the market to prevent resistance from arising. This poses a serious challenge in attempting to solve the AMR crisis through novel drug development as the cost of R&D cannot be reimbursed. This problem has plagued the field and depleted the potential pipeline of opportunities, causing humans to fall behind ever-evolving bacteria in the AMR race.
Repurposed DNA-modifying drugs can eliminate microbial defences, effectively re-sensitising bacteria to the antibiotic.
New approach to an established challenge
DNA sequencing costs continue to drop, enabling genomic research to become a growing and accelerating field. As we have seen through the Covid-19 pandemic, pathogen sequencing enables a rapid and accurate diagnosis of specific strains, which can support drug discovery and treatment through the translation of genetically encoded targets and susceptibilities. Bioinformatic analyses can highlight weaknesses in bacterial DNA that we can exploit to lower defences and overcome antimicrobial resistance.
Identification of genomic vulnerability can enable novel, genetically validated modulators to supplement antibiotics at reduced costs and with a reduced likelihood of attrition from target to medicine. Many pharmaceutical companies will not accept targets into their early pipelines without a demonstration of genetic validation. By taking this new approach and focusing on genetic vulnerabilities as opposed to expressed targets, it should be possible to raise the barrier to new resistance arising, which should alleviate the issue and give healthcare a concerted step forwards.
Combination therapy, reinvigorating antibiotics
Repurposed DNA-modifying drugs can eliminate microbial defences, effectively re-sensitising bacteria to the antibiotic. This means that rather than trying to find a new drug, we can simply reinvigorate existing drugs by lowering or even eliminating resistance in the target pathogen. The solution to AMR is already here; industry collaborations and partnerships with academics and SMEs can identify these weaknesses and offer the drugs required to exploit them. Repurposing existing drugs in novel combinations significantly reduces the R&D cost, presenting an economically viable way to overcome AMR and save lives.
