Guido Krenning’s super molecule
Four diseases, one cure
It took ten years of research and 238 iterations of the same molecule, they’re close to reaching the finish line. Once they pass it, molecular biologist Guido Krenning will have developed a new drug that can be used against Alzheimer’s. As well as heart failure. And kidney failure. And even the pulmonary disease COPD. ‘We’re hopeful that Sul-238 can treat all these diseases’, Krenning says confidently.
This would be a breakthrough for the medical community, because in spite of decades of global research, there still isn’t a drug on the market that can truly treat Alzheimer’s. And while doctors can prescribe bronchodilators to help with COPD, there currently is no cure for this disease.
But Krenning, who in addition to his work as a researcher at the UMCG also works as chief scientific officer at pharmaceutical company Sulfateq BV, is confident that he and his colleagues will succeed where others have failed. ‘While the diseases may not have much in common on the surface, they overlap quite a bit on a cellular level’, he says. That’s why this one drug could help with four different diseases.
Hibernation
The group was inspired to create Sul-238 by the animal world, says Krenning, who also collaborated with pharmacology professor and hibernation expert Rob Henning. ‘When animals enter hibernation, their bodies release a lot of chemicals that damage their cells. But once hibernation is over, these animals recover from the damage without any lasting consequences.’
We take observations from nature and turn them into new drugs
Human beings don’t have this ability. ‘If you lower the body temperature and the metabolism in human cells, these cells will die off because they can no longer produce energy’, says Krenning.
Animals use vitamin E to prevent this from happening. This vitamin plays an important role in energy production in the cell and ensures this production continues even when the cell is exposed to harmful chemicals. ‘The mechanism the animals use to lower their body temperature and metabolism is the basis for our drug’, Krenning explains. ‘Here at Sulfateq, we take these observations from nature and turn them into new drugs.’
Mitochondrion
This enabled the researchers to develop a molecule that can hopefully cure diseases caused by issues in the cell’s energy production: Sul-238.
The molecule targets what might just be the most important part of the cell: the mitochondrion, also known as ‘the powerhouse of the cell’. In a complex chain of various molecules, the mitochondrion uses oxygen to create energy.
This process creates a by-product: reactive oxygen species, or ROS. Under normal, ‘healthy’ circumstances, ROS doesn’t have the opportunity to accumulate in the mitochondrion. When this does happen, the mitochondrion is damaged and the cell dies as a result.
‘Sul-238 is essential to maintain your mitochondria’, says Krenning. ‘It prevents the production of ROS, which means energy products can continue as normal. This keeps the cell alive.’
Human trials
Damaged mitochondria are the source of many conditions: not just heart and kidney failure and COPD, but also Alzheimer’s, the disease Krenning is most focused on.
Not even the highest dose has led to any side effects
‘However, we don’t know if the process which causes the damage to the mitochondria is the same in all these diseases’, Krenning offers cautiously. But that doesn’t change anything about his ultimate goal to treat various diseases with this same drug. The first results from the animal trials seem good. ‘You always have to wait and see how people will react to a drug as compared to the animal test subjects.’
After ten years of experiments, the end is in sight. In the case of Alzheimer’s, they’ve even taken the first step towards testing on healthy people, also known as a Phase 1 study. ‘In this trial, we’re giving people an increasingly higher dose of Sul-238 to see what kind of side effects, if any, it has’, says Krenning. ‘Right now, we’ve administered the highest dose we’re allowed to give, and we haven’t seen any side effects yet.’
Stop memory loss
Once this phase has been successfully concluded, they can move on to a Phase 2 study: research on real Alzheimer’s patients, which can take at least four to five years.
It’s going to be a difficult phase, says Krenning. ‘Alzheimer’s is a difficult disease, because its main characteristic is memory loss. So, until someone starts losing their memory, they don’t officially have Alzheimer’s’, he explains. ‘At some point, a patient will forget someone’s name once a month. Then it becomes twice a month, then once a week. And only then do they get an Alzheimer’s diagnosis.’
He hopes that Sul-238 can stop this memory loss, to prevent people from descending into full dementia. But whether people will actually be able to recover from Alzheimer’s remains to be seen. So far, no drug has proven effective against the disease. ‘We don’t know to what extent the brain has regenerative abilities, because no one’s ever been able to make it regenerate’, he says. ‘You can cure diabetes type 2 by changing your lifestyle. But no one knows if there is any regenerative potential when it comes to Alzheimer’s.’