Hibernation enables some animals to overcome periods of extreme cold or food scarcity. During hibernation, these animals lower their metabolism, body temperature, breathing and heart rate, protecting them from organ damage. Maintaining the function of the mitochondria, the ‘powerhouses’ of the cell, is crucial for hibernating animals to safely get through the winter.
Mimicking the protection of hibernators
Humans are unable to protect their organs during the extreme conditions of hibernation, leading to substantial organ damage. Hjalmar Bouma is investigating the effects of activating hibernation mechanisms in non-hibernators. Bouma: ‘I am convinced that this may eventually lead to the development of new human medicines. We want to replicate the protection mechanisms of hibernators. An important part of this is the optimisation of the function of mitochondria. This can help us to protect human organs from organ failure.’
Hibernation medicine prevents cell death and organ failure in mice
The disruption of mitochondrial function plays an important role in organ failure in sepsis. Bastiaan Star is one of the researchers directly involved in the research into the effects of a newly developed 'hibernation medicine' called SUL-138. This substance is based on molecules that hibernators use to prevent organ damage. Star: ‘Treating cells with this medicine ensures that the mitochondria retain their function, and it prevents cell death during extreme hypothermia. We studied this by putting the cells in the refrigerator. It also prevents cell death when we mimic sepsis in the cells, which we demonstrated in mice in the laboratory. In mice with sepsis, treatment with the new medicine inhibits inflammation and protects against kidney damage.’
Effectiveness in humans?
Before a medicine can be used in patients, extensive safety and side effect tests at the cell level and on laboratory animals must be performed. These tests have now been completed without any problems. The safety of the medicine is currently being tested in volunteers, under strict conditions and in low doses; this is taking place in so-called phase 1 studies. If SUL-138 proves to be safe, follow-up studies on its effectiveness in humans will follow. The researchers expect to reach this stage in about a year.
Finding the right patients via the Acutelines biobank
One of the challenges is to select patients with sepsis who could benefit most from this medicine at an early stage. Based on medical data and biomarkers in the blood, research is now being carried out to select the most appropriate treatment for each patient: ‘personalised medicine’. According to Bouma, the UMCG has the right infrastructure in place for this research. ‘Over the past few years, we have created the Acutelines biobank within the emergency department. This will enable us to conduct large-scale research into the origin and treatment of acute diseases. Acutelines contains the collected data and body materials from acutely ill patients. This also includes many data from patients who have been admitted to the emergency department with sepsis.’
Research needed for use in patients
Bouma expects that in future, Acutelines and his research team will have an important role to play in verifying the effectiveness of the new medicine in patients with sepsis at the emergency department. Partly due to the knowledge gained from Acutelines, patients could be selected early based on the potential development of organ damage; they would therefore be the first to be eligible for SUL-138. Bouma: ‘A lot more research is needed to prevent organ damage and death due to sepsis. We expect the new medicine to make a vital contribution. I sincerely hope that it will be possible to acquire sufficient research funding for this project.’
About this research
The research is the result of a collaboration between the UMCG and Sulfateq. The results of the study are open access and available. Hjalmar Bouma previously talked about the background of his research into hibernation in an episode of NPO Atlas (in Dutch).