Faculty researchers have developed an artificial intelligence (AI) method to help them identify potential new drugs for Alzheimer’s disease. The new drug seems to be more precise. No side effects have been documented in tests with worms and mice.
Waste management of cells is destroyed by Alzheimer’s disease
One of the causes of Alzheimer’s disease is the degeneration and loss of nerve cells in the brain with age. A cell is like finely tuned machinery. The cell needs energy to perform its tasks. Energy comes from energy factories called mitochondria.
In young, healthy cells, old or damaged mitochondria are removed from the cell in a process called mitophagy. The research group found that as we age, we have more broken mitochondria and the cells will no longer be able to eliminate them all. A buildup of broken mitochondria obstructs the cell’s ordinary processes and eventually the cell will die.
– The cells need the energy generated by the mitochondria to clean up this “waste”. Just like a machine will stop working if it is not maintained, says Associate Professor Evandro F. Fang, the research group leader.
Fang leads an international research group at the University of Oslo’s Institute of Clinical Medicine and Akershus University Hospital.
A new way to treat Alzheimer’s disease
A potential new method for treating the disease is described by Fang’s group in a new study:
We may be able to reduce or stop disease progression with the patient. We can do this by increasing the cell’s ability to clean itself.”
Evandro F. Fang, Associate Professor
With the clogging of the machines being part of the problem, the researchers had to find a way to speed up the cleaning process. They looked into the use of so-called mitophagy inducers. The idea was to find a way to increase the level of waste management in the patient’s brain cells.
– We can compare it to hiring additional staff to eliminate a cleaning backlog in a factory, says Fang.
Fang’s group described how it might be possible to find a way to stimulate cells’ own self-cleaning system in 2019.
Treatment may improve other organs
Rebooting mitophagy provides the patient with several benefits: it will increase waste removal from brain cells, and the cleansing process will be more efficient on its own. It may also increase cleansing in other organs, not just the brain.
– By increasing mitophagy, we can also improve the quality of other organs, such as their heart and muscles. A stronger body is important for reducing the effects of the disease, notes Fang.
Using AI to find potential candidates for a new drug
It takes a lot of time and effort to develop a new drug, and it’s a very expensive process. The researchers wanted to find substances that could induce the cleansing process. They used AI to search for substances similar to known mitophagy inducers.
The computer program scoured a large catalog of substances and identified two candidates, Rhapontigenin and Kaempferol. They used mice and nematodes, a type of worm, to document whether using these substances on their nerve cells inhibited memory loss.
– We spent three months searching a library of about 3000 known substances that induce mitophagy. If we had used traditional techniques to discover a new drug, it would probably have taken more than three years to find potential drug candidates,” says Fang.
Researchers have filed a patent on the new drug for Alzheimer’s disease
Fang and his colleagues filed a patent on Rhapontigenine for the treatment of Alzheimer’s disease. They are currently working to describe both how rhapontigenin and kaempferol can help us delay the progression of memory loss and how they can help us reduce the progression of the disease when it has occurred. Additionally, they will also describe the in-depth molecular mechanisms that help Kaempferol and Rhapontigenine to induce mitophagy.
The compounds have not yet been tested in humans, so there is still much to be done.
-We are now using AI to propose small structural modifications to these candidate compounds. We want to make them safer and more effective for treating Alzheimer’s disease, Fang says.
The project is an international multi-institutional project with major collaborators from:
- University of Oslo, Norway
- The University of Macau, China
- MindRank AI Ltd, China
- National and Kapodistrian University of Athens, Greece
- Imperial College London, United Kingdom
- University of Alabama at Birmingham, USA
- The National University of Singapore
Xie, C. et al. (2022) Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Biomedical engineering from nature. doi.org/10.1038/s41551-021-00819-5.