‘Kidney tubule cells from hibernators have an increased resistance to oxidative stress compared to non-hibernators. Based on our research into hibernation, we have identified a series of chemical entities which are capable of protecting the mitochondria in non-hibernating species, just like hibernating species do’, says Pieter Vogelaar, chief operational officer and researcher at Groningen-based biotech company Sulfateq B.V. ‘These 6-chromanols might offer great therapeutic benefit in diseases where mitochondrial function is impaired.’ To prevent acute kidney injury during open heart surgery, for instance.
text: Ronald Vermeer
Pieter: ‘When the blood circulation is taken over by a heart-lung machine during open heart surgery, it reduces the blood circulation to certain organs, including the kidney, thus limiting the transport of oxygen and glucose for energy production. Kidney cells are extremely sensitive to a lack of oxygen and glucose due to their high metabolic activity. The hibernator kidney maintains synthesis of ATP, an important source of energy, even when blood gets flowing when they warm up. Non-hibernators also have this capacity, but generate many harmful byproducts like reactive oxygen species while doing so.’
Pieter Vogelaar is researching the prevention of Acute Kidney Injury (AKI) using scientific insights from hibernation research under the Dutch Industrial Doctorates pilot programme. The Industrial Doctorate grant was awarded to Prof. Rob Henning, pharmacologist at the UMCG, last August. Within the programme, a PhD student carries out his or her research both at the knowledge institution and the participating company. Pieter Vogelaar, put forward as a candidate by the UMCG and Sulfateq, will carry out his thesis research at both sites.
Pieter: ‘Acute Kidney Injury is a critical clinical syndrome characterized by the rapid loss of the kidney's excretory function and is typically diagnosed by the accumulation of end products of nitrogen metabolism (urea and creatinine). Mitochondrial dysfunction and damage of renal tubular cells, culminating in a state of oxidative stress, is reflected by the increased excretion of mitochondrial DNA in urine, an established feature of AKI. A natural de-fense mechanism against such oxidative stress-induced organ damage can be found in hibernating animals.’
The ultimate aim of Vogelaar’s thesis is to maintain the renal energy production and preclude kidney failure by boosting the renal power plants, the mitochondria, with small molecule drugs. Pieter: ‘The main focus of my research is the development of mitochondrial medicines to prevent AKI. Herein, I will use several pre-clinical cell- and animal models to investigate how mitochondrial health relates to the development of kidney injury. These insights can be used to screen for new drugs, a second generation of SUL compounds perhaps.’
By working closely together in their cutting-edge research, Sulfateq and the University of Groningen have brought an intervention for AKI one-step closer. Pieter: ‘The next step is the transition from the pre-clinical into the clinical phase: To develop a drug for the prevention of AKI. The development of new medicines by further developing a platform that has the ability to quickly go from discoveries in fundamental hibernation research to preclinical development.’
Besides preventing Acute Kidney Injury, the fundamental research based on hibernation may offer therapeutic benefits to prevent other disease as well, including Alzheimer and Diabetes Type 2. Pieter: ‘If you closely examine the hamster's brain during hibernation, you will find brain damage similar to the damage observed in the brain of patients with Alzheimer's disease. Interestingly, this damage is completely restored when the animals exit hibernation’
‘Before going into hibernation, some species eat so much that they become obese and their blood glucose rises to a level that is comparable to the blood sugar level of a Diabetes patient. When they wake up months later, their weight and blood sugar value is completely normal again. Notably, where swings in body-weight and high blood sugar levels may cause diabetic complications in patients, these hibernators do not show any sign of illness,’ says the young PhD candidate. Pieter: ‘Hibernator species are a good example to illustrate how good a hibernator is in the reversal of syndromes that we as humans can’t recover from.’
For more information, you can contact Prof. Dr. Rob Henning via e-mail or Pieter Vogelaar via the Sulfateq website or twitter via @Sulfateq
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