Gene therapy and medication can provide certain beneficial effects of physical exercise

Jose Bianco Moreira and the CERG research team from the Norwegian University of Science and Technology (NTNU) are now convinced that medication and gene therapy can be used to achieve some of the positive health benefits of physical exercise.

Gene therapy and medication can provide certain beneficial effects of physical exercise
The picture shows heart cells formed by stem cells. The cell nucleus appears blue and stem cells are green. NTNU researchers have identified a protein that heart-diseased rats are deficit in, but which increases when the rats have been on an exercise regimen. Photo: Norwegian University of Science and Technology.

We’re not talking about healthy people and everyone who can exercise. They still have to train, of course,” Moreira stated. He and his collaborators from the Department of Circulation and Medical Imaging at NTNU are investigating the impact of exercise on human cells.

Those who cannot

But some people can’t train, or only in a limited way. This could include individuals who’ve been in accidents, who are in wheelchairs, or who have diseases that prevent the possibility of physical expression. We want to create hope for these folks.”

Jose Bianco Moreira, Scientist, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology

He continued, “A small group of healthy people out there also obtain very little effect from physical exercise—so-called low responders—and would benefit from a method that worked at the cellular level.”

Cells are the key

While plenty of research works have confirmed the health benefits offered by physical exercise, very little is known about what actually occurs in the cells that offer positive effects.

International research in this field is brand new. We’ve barely scratched the surface. We think increasing our knowledge about what happens at the cellular level will be important for discovering medications and treatments for heart disease. My group studies genes, proteins and mitochondria that produce energy and are key for chemical processes in the cells.”

Jose Bianco Moreira, Scientist, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology

Gene therapy already in use

According to Moreira, gene therapy is the most effective technique for recreating the health benefits that people usually get from physical exercise.

A drug that makes use of gene therapy is already being used for spinal muscle atrophy—a serious disorder that results in muscle wasting. The medicine uses an innocuous virus to deliver a copy that substitutes the network of impaired motor neurons in patients.

This kind of treatment can improve or suppress gene expression. But this drug is extremely costly and has not been attempted for heart disease, for instance.

CRISPR is coming

According to Moreira, CRISPR will be the go-to gene therapy method in the days to come. He believes that this technique of editing the genes will redefine a whole lot of disease treatments.

CRISPR is easier to use, faster and cheaper than today’s gene therapy, which only attenuates or enhances the expression of a gene. CRISPR’s potential is almost limitless. It can alter the gene itself. The parts of the gene that don’t work properly are replaced with well-functioning parts, Moreira added.

Experiments performed on mice and rats have demonstrated that the technique indeed works. In addition, experiments have also been carried out on human cells in laboratory settings to prove the effectiveness of the CRISPR technique, but it is yet to be tested on human beings.

CRISPR still has to be tested in large clinical studies. I’d be optimistic if I say gene editing will come into regular use in 10-15 years,” added Moreira.

Permanent cure

The research team of Moreira has applied the CRISPR technique in this analysis, but the study results are not completely ready for publication.

We believe gene therapy is the most powerful method because patients don’t have to take a pill every day. Usually, gene therapy changes the gene forever, perhaps with an injection or two. The challenge is to find the right gene that needs change, and an effective method to repair it,” Moreira added.

The NTNU team is targeting the heart. They have detected a protein that is absent in rats afflicted with heart disease, but the level of the same protein increases when the animals are subjected to training.

By increasing the amount of this protein through gene therapy, we’ve managed to strengthen the muscle cells and have replicated some of the positive effects of physical exercise,” Moreira further stated.

Medicines

Drugs are another viable technique of imitating the positive effects of exercise. Certain present-day medications may also be able to reproduce some of the beneficial effects on the heart.

The research now has powerful technology platforms to find possible other uses for medicines we already have. One problem, of course, is that medicine is chemistry that affects the whole body, not just the organ you want to help. Something that’s good for the heart could be detrimental for the liver, for example. Compared to gene therapy, though, the potential for medications is much more limited.”

Jose Bianco Moreira, Scientist, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology

Finding “attack targets”

When the NTNU researchers initiated their analysis, they were clueless about which kinds of genes were influenced by exercise. The team carried out experiments, in which rats that have heart defects underwent training.

Later, the researchers removed and analyzed the animals’ hearts and subsequently compared these organs with those taken from untrained rats that also had heart disease. Later, the hearts of both untrained and trained rats with heart disease were evaluated against healthy rat hearts.

We observed that genes were altered in the diseased hearts, but discovered that some of them were repaired in the rats that had trained. This way, we find genes that we can target. Through our measurements, we can find out exactly what training changes at the cellular level,” concluded Moreira.

The NTNU group is partnering with Johan Aurwerx and his team from the École Polytechnique Fédérale in Lausanne.

Source:
Journal reference:

Moreira, J. B. N., et al. (2020) Exercise and cardiac health: physiological and molecular insights. Nature Metabolism. doi.org/10.1038/s42255-020-0262-1.

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