Consortium led by Markus Weingarth awarded €1.5 Million to tackle antibiotic toxicity

Fundamentally understanding why some antibiotics turn out to be toxic is now a major step closer, thanks to a €1.5 million grant awarded to biochemist Markus Weingarth. Using the grant, Weingarth will lead a research project to reduce the risk of kidney damage caused by antibiotics. The grant is provided by the Dutch Research Council (NWO).

Tackling antibiotic toxicity is the focus of the new research project led by Markus Weingarth, which has just received a Knowledge and Innovation Community (KIC) grant. This toxicity, which could lead to kidney damage, is a major hurdle in developing new treatments.

Understanding what causes kidney damage is extremely challenging, yet crucial for improving antibiotics

“Most drugs don't fail because they are ineffective,” says Weingarth. “They fail because of toxicity. Kidney damage is a major reason for that. Understanding what causes kidney damage is extremely challenging, yet crucial for improving antibiotics.”

Uncovering molecular rules

By studying the chemical interactions that determine how antibiotics behave in the body, Weingarth’s team hopes to predict and prevent toxic side effects. If successful, this project could save millions in research costs and improve the safety of antibiotics worldwide.

If we fundamentally learn what causes the toxicity, we may be able to predict it much earlier in the development process

“Normally, this type of toxicity only comes to light when the drug is clinically tested on subjects,” says Weingarth. “This is at a very late stage in drug development. If we fundamentally learn what causes the toxicity, we may be able to predict it much earlier in the development process.”

Antibiotic resistance

Weingarth’s team will begin by focusing on the antibiotic teixobactin, a promising new treatment currently in development. Teixobactin shows potential in combating infections caused by bacteria that have developed resistance to existing antibiotics. The project will also explore ways to improve cilastatin, compound known to inhibit kidney toxicity.

Complex challenge

Weingarth stressed the complexity of the challenge. “It’s much harder to determine toxicity than it is to measure how well an antibiotic works against bacteria. For instance, some antibiotics need a positive electric charge to be effective, but that same charge also drives kidney toxicity. Finding the right balance is very difficult.”

Pharmaceutical companies have struggled to address this challenge on their own. Furthermore, kidney toxicity is highly complex and poorly understood, requiring specialized expertise in molecular biology and chemistry to investigate thoroughly.

Industry partners

Weingarth’s consortium includes academic and industry partners. In addition to Utrecht University’s expertise in structural biology, Leiden University’s medicinal chemistry expert Professor Nathaniel Martin will play a major role. The project also involves two industry partners: Cell4Pharma, a Dutch company specializing in drug-induced toxicity research, and NovoBiotic, a US biotech company.

“Collaboration is essential for this project,” says Weingarth. “Our partners bring vital expertise, from understanding the biological mechanisms to developing safer drugs.”

About the KIC grant

The KIC grant is designed to foster partnerships between academic researchers and industry experts. The grant is awarded by the Dutch Research Council (NWO).