U. of Virginia research highlights limitations of pharmacological studies aimed at treating humans

A groundbreaking discovery by the University of Virginia School (UVA) of Medicine has challenged a long-held belief in drug development that the drug transporter in blood, known as albumin, mimics the behavior of human blood in lab models. 

“The cross-drug interaction is often discovered during clinical trials and sometimes only when new medicines are on the pharmacy shelves,” said Wladek Minor, a Harrison Distinguished Professor in UVA’s Department of Molecular Physiology and Biological Physics, in a UVA news release.

Research from Minor and collaborators revealed that non-human albumins, such as bovine albumin from cattle, and animal models, such as lab mice, may not produce reliable results for developing drugs for humans.

The researchers investigated the common nonsteroidal anti-inflammatory drug (NSAID) ketoprofen and found it produced inconsistent interactions with human albumin and other mammalian albumins as different albumins binded with the drug in different locations. 

Co-author Alan Stewart, a Ph.D, from the University of St Andrews, said the work “highlights a need for caution when using non-human albumins or animal models in drug development.”

The study was published in the scientific journal IUCrJ and accompanied by an editorial, shedding light on the importance of the work, with regards to the development of safer drugs. 

Mateusz Czub, a UVA Ph.D recipient currently at Paul Sherer Institute in Switzerland and Ivan Shabalin, a Ph.D and alumnus of Minor’s lab, currently are working on a precision medicine approach to oncology therapeutics at IDEAYA Biosciences in San Francisco. Minor and Shabalin were part of the research team. 

The researchers have called for additional studies looking into how other drugs bind with albumin and advise scientists to assess the suitability of particular albumins for their research to reduce the risk of unexpected and unwanted drug interactions.

“We hope that this work will help researchers understand the limitations of pharmacological studies aimed at treating humans but that are based on other organisms,” Minor said.

Minor has trained more than 120 students, who have become prominent scientists at top universities, and industry leaders at companies such as Google. 

He has also assisted in developing state-of-the-art software, data management and mining tools that have been used in new albumin research as co-founder and board member of HKL Research.