“Preclinical research serves as a bridge to new medicines,’’ says North-West University (NWU) academic Prof Rose Hayeshi, associate professor and director of the DSI/NWU Preclinical Drug Development Platform (PCDDP).

Preclinical drug development is one of the stages of development for new medicines and her specific interest is in drug metabolism.

Prof Hayeshi says the development of new medicines can be divided into two broad areas – discovery and development.

“Discovery is the process of finding or designing new molecules that could someday lead to candidate medicine, and development is the process of rigorously testing a medicine candidate for safety and efficacy to bring a new medicine to market. Preclinical development is the first stage in development and forms the bridge between the discovery and development stages,” she explains.

“Humanised” mice used to predict body’s responses

“Medicines that enter the human body are seen as a threat which then leads to the body trying to remove or alter these substances using enzymes such as cytochrome P450 enzymes or CYPs. This is termed drug metabolism.

“It is therefore important to understand the role of CYPs during development of new medicines to predict the dosage and dose frequency. Hence during the preclinical testing stage, i.e., before the new medicine is tested in humans, experiments are done on mice to determine these predictions.”

As mouse CYPs differ from human CYPs, Prof Hayeshi’s research focuses on focuses on using humanised mice, engineered to express human CYPs, to predict how human CYPs would interact with medicines under development or medicines used in combination.

In resource constrained populations, the use of medicinal plant products for the management of diseases is common and may be used in combination with conventional treatment, she says. Some of these plant products have been reported to alter the function of CYPs.

“There is, therefore, a risk for interactions in the co-administration of conventional treatment such as prescription medicine with the alternative therapies, termed herb-drug interactions.”

African medicinal plants have a place

Prof Hayeshi is currently conducting research with a humanised mouse model expressing a human CYP to investigate herb-drug interactions in the co-administration of conventional medicines for infectious diseases such as TB, malaria and HIV, with medicinal plant products used for managing these diseases.

She has recently graduated one MSc student on a project evaluating potential herb-drug interactions between Efavirenz, a medicine used for the management of HIV, and African medicinal plants, using the humanised mouse model.

Ultimately, Prof Hayeshi has a vision of enhancing preclinical drug development capability in Africa by providing more translational preclinical models and by training and mentoring researchers.

More about Prof Hayeshi

Prof Hayeshi holds a PhD in biochemistry with experience in the field of pharmaceutical sciences gained through training and research positions held in Zimbabwe, Sweden, the Netherlands and South Africa.

She also has experience as a study director for preclinical testing in compliance with Good Laboratory Practice (GLP) guidelines. Her research interests are in preclinical testing for drug development as well as in drug metabolism and drug transport. She designs and manages preclinical animal studies for the South African pharmaceutical industry and academic researchers.

Prof Hayeshi has co-authored 25 publications and two book chapters. She contributes to the strengthening of science through participating as an external evaluator for the clinical committee of the South Africa Health Products Regulatory Authority, and by membership in national science associations. 

She is a member of the South Africa Young Academy of Sciences, a fellow of the Africa Science Leadership Programme and an alumnus of the DAAD Dialogue on Innovative Higher Education Strategies Programme. Her national standing was recently recognised as a finalist in the 2019/2020 NSTF-South 32 Awards.

Prof Hayeshi works in interdisciplinary and interinstitutional collaborative teams involved in different aspects of drug and vaccine development. For example, she assisted in coordinating the preclinical trial on a new Covid-19 DNA vaccine candidate in 2021, and she is currently responsible for coordinating the preclinical trials for the Covid-19 mRNA vaccine being developed by Afrigen Biologics.

Prof Rose Hayeshi