Innovative technique’ may lead to improved drugs for cancer, Alzheimer’s disease and lung diseases

A class of molecules may be able to accelerate DNA repair and help to treat diseases such as Alzheimer’s, according to new research published in the journal Science.

Researchers at Karolinska Institutet in Sweden have improved the ability of a protein to repair oxidative DNA damage and created a new protein function. They believe their innovative technique could lead to improved drugs for diseases involving oxidative stress, such as cancer, Alzheimer’s disease and lung diseases.

Four chemistry students from the University of St Andrews helped to discover this novel information in a joint research project carried out as part of the Industrial Placement year of the students’ MChem degrees.

The compounds identified by the researchers could slow down the ageing process

In the study, the researchers improved the function of a protein called OGG1, an enzyme that repairs oxidative DNA damage, implicated in ageing and diseases such as Alzheimer’s disease.

The researchers then examined how examined how catalyst molecules bind to OGG1 and affect its function in cells. One of the molecules proved to be of particular interest.

€œWhen we introduce the catalyst into the enzyme, the enzyme becomes ten times more effective at repairing oxidative DNA damage and can perform a new repair function,€ says the study’s first author Maurice Michel, assistant professor at the Department of Oncology-Pathology, Karolinska Institutet.

The discovery opens new avenues for the treatment of diseases which result from DNA damage, such as Alzheimer’s disease, certain cancers and lung conditions, and the compounds they have identified should slow down the ageing process.

The discovery €œmay shift the way we approach medicinal chemistry€

Professor Thomas Helleday at the Department of Oncology-Pathology, Karolinska Institutet and the study’s last author also sees broader applications, where the concept of adding a small catalyst molecule to a protein is used to improve and change other proteins as well.

€œWe believe that this technology could instigate a paradigm shift in the pharmaceutical industry, whereby new protein functions are generated instead of being suppressed by inhibitors,€ he said. €œBut the technique isn’t limited to drugs. The applications are virtually unlimited.€

Nicholas D’Arcy-Evans, co-author and chemistry student at the University of St Andrews said: €œTo be involved in work like this was far beyond anything I expected during the placement year. It was fantastic to learn from and work alongside leading scientists to answer such a challenging question.

€œWe believe that the discovery may shift the way we approach medicinal chemistry €“ where drugs are designed for enzyme activation, rather than inhibition. I’m excited to see where this goes and how it can help patients in the future.€