Investigating why mitochondrial diseases take markedly different clinical courses

The drug candidate now under development offers hope for a treatment that targets the underlying cause of certain severe mitochondrial diseases, rather than merely alleviating symptoms. The discovery builds on long-term basic research and extensive team-based collaboration, often conducted in partnership with international researchers. 

The first phase of the clinical trial, in which the drug candidate is being tested in healthy volunteers, is currently nearing completion. If this phase proves successful, the next stage of clinical testing will begin. The treatment will then be evaluated in patients with mutations in the POLG gene and compared with placebo. 

For the research group, the clinical trial marks a critical next step. At the same time, development remains at an early stage. Clinical drug development follows a strictly regulated, stepwise process in which each phase must be carefully evaluated before the next can proceed. 

“This is the result of many years of collaborative work. To now see our basic research move into clinical application is immensely rewarding for the entire team,” says Maria Falkenberg, Professor of Laboratory Medicine at the University of Gothenburg. 

Markedly different clinical courses 

The researchers are now moving forward with studies designed to clarify why mutations affecting the same gene can lead to such pronounced differences in disease severity. Some children develop disease at birth, rapidly become critically ill, and die, while others live well into adolescence or adulthood and develop a more slowly progressive disease course, with symptoms such as muscle weakness, epilepsy, or visual impairment. 

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“This is one of the key questions driving our research. We want to understand the mechanisms that determine whether the disease becomes very severe early in life or progresses slowly over several decades,” says Maria Falkenberg. 

The research group is investigating how different mutations affect the function of the enzyme that is essential for cellular energy production and how these effects interact with other cellular factors. This knowledge is crucial both for deepening understanding of these disorders and, in the longer term, for determining which patients are most likely to benefit from the treatment now under development. 

Securing time for sustained research 

In 2026, Maria Falkenberg will be awarded the Torsten Söderberg Academy Professorship in Medicine. The professorship allocates university resources to support continued research within the group and enables her to devote herself fully to research for several years. 

“It is incredibly rewarding to see many years of joint effort now advancing to the next phase. At the same time, we are far from finished. This opportunity allows us to sustain our long-term efforts, both to develop treatments and to understand these diseases at a fundamental level,” she says.