Science
Guido Krenning Photo by Reyer Box
At first glance, Alzheimer’s, heart failure, kidney failure and COPD have little in common. However, medical researcher Guido Krenning and his team hope to bring a drug to market that will treat the common cause of these diseases.
By Wouter ten Cate
It took ten years of research and at least 238 versions of the same molecule, but now the finish line seems to be finally in sight. And once it passes, molecular biologist Guido Krenning has developed a new drug that could be used against Alzheimer’s. And heart failure. And kidney failure. And COPD lung disease. “With Sul-238 we are hopeful that we can treat all these diseases,” Krenning says confidently.
And that would represent a breakthrough in the medical world, because despite decades of research around the world, there is still no very good medicine on the market that can fight Alzheimer’s . And although doctors can prescribe bronchodilators for COPD, there is no cure.
But Krenning – who, in addition to his work as a researcher at the UMCG, also believes senior scientific officer he is from the pharmaceutical company Sulfateq BV – may he and his colleagues be successful. ‘These diseases don’t look like each other beforehand, but they overlap if we move into a little more than our cells,’ he says. And as a result, that same substance can have a positive effect on four diseases.
hibernation
The inspiration for Sul-238 came from the animal world, says Krenning, who also worked with professor of medicine and hibernation expert Rob Henning. “When animals hibernate, many substances are released that damage the cells. But once hibernation is over, these animals will recover from the image of this damage without suffering any negative effects.’
We translate ideas from nature into new medicines
People can’t do that. “If you lower the body temperature and the metabolism of human cells, those cells would die because they could no longer produce energy,” says Krenning.
Animals use vitamin E to prevent this. The vitamin plays an important role in making energy in the cell, but it also ensures that this product is maintained when the cell is exposed to harmful substances. “The mechanism these animals use to reduce body temperature and metabolism is the basis of our medicine,” Krenning explains. ‘What we do at Sulfateq is to translate these kinds of ideas from nature into new medicines.’
Mitochondrion
And so the researchers were able to develop a molecule that could hopefully treat diseases caused by problems with cellular energy production: Sul-238.
Perhaps the molecule targets the most important part of the cell: the mitochondrion, also known as the ‘powerhouse of the cell’. In a complex series of all kinds of different molecules, this creates energy through the use of oxygen.
This produces reactive oxygen compounds as a by-product, better known by the English name ROS (reactive oxygen species). Under normal, ‘healthy’ conditions, ROS have no chance of accumulating in the mitochondrion. When this happens, damage occurs to the mitochondrion, leading to the death of the cell.
“Sul-238 is important for maintaining your mitochondria,” Krenning said. “It prevents the production of ROS, so that energy production proceeds normally. This will keep the cell alive.’
Research on people
Damage to the mitochondria is the cause of many conditions: heart failure, kidney failure and COPD, but also Alzheimer’s, the disease that Krenning first focused on.
With the highest dose we do not see any side effects yet
‘We don’t know if the way in which this mitochondrial damage occurs is the same in all these diseases,’ said Krenning carefully. But that does not detract from his ultimate goal of treating multiple diseases with the same drug. The first results based on animal studies are favorable. “But we always have to wait and see how people will eventually react to it compared to laboratory animals.’
After ten years of testing, it is now almost time. In the case of Alzheimer’s, even the first step towards research on healthy people has been taken, also known as phase 1 research. ‘People are receiving increasingly higher doses of Sul-238 to see do side effects arise,’ says Krenning. ‘With the highest dose that we can and that we want to administer, we still do not see any side effects.’
Stop memory loss
If this phase is successfully completed, a final phase 2 study is in sight: research with real Alzheimer’s patients that will also take at least four to five years.
That can be difficult, too, Krenning admits. “Alzheimer’s is a difficult disease because it is characterized by memory loss. So until you develop memory loss, you don’t officially have Alzheimer’s,” he explained. ‘At some point someone forgets his name once a month. That will be twice a month, then once a week. And only then will Alzheimer’s be diagnosed.’
He hopes that with Sul-238 he can stop memory loss, so that people will not be completely depressed. But the question remains whether it is possible to get back. So far, no drug has been effective against Alzheimer’s. “We don’t know how much the brain can regenerate, because that has never happened,” he says. “You can get rid of type 2 diabetes if you change your lifestyle -life. But no one knows if this regenerative capacity is present in Alzheimer’s.’
2024-10-28 07:49:00
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