Preventing Parkinson’s disease with a gene?

Although we have known about Parkinson’s disease for more than 200 years, its exact causes have still not been identified and there is no cure. It is the most common neurodegenerative disease after Alzheimer’s: in Switzerland, it affects around 15,0000 people. In work published in March, a team of scientists from the University of Geneva (UNIGE) discovered a gene in the fruit fly that, when modified to be more active than normal, protects neurons against Parkinson’s. .

A gene with a neuroprotective role

This gene, called iron2, was first discovered during a previous search. In the fruit fly, a mutation makes it inactive and leads to disorders associated with those of Parkinson’s disease. However, this does not mean that the mutation is directly responsible for the disease. Subsequently, scientists tried to « overexpress » the gene iron2 in the fly to be more active and produce more regulatory proteins. Result: “The flies were protected against factors responsible for Parkinson’s disease, such as ‘oxidative stress’ or genetic mutations. A greater amount of iron2 has therefore prevented neurodegeneration,” says Emi Nagoshi, associate professor at UNIGE and head of the behavioral neuroscience and neurodegeneration laboratory, who conducted the research.

The research team showed that the healthy version of iron2 plays an important role in the survival of dopamine neurons, those that are destroyed in Parkinson’s disease. “This gene is involved in the regulation of other genes, which then go on to maintain the health of neurons. More precisely at the level of the mitochondria, the cell’s small power stations,” continues Emi Nagoshi. In the disease, mitochondria are damaged, causing neurons to die. Scientists have also discovered that this gene has an equivalent in mice and humans, NATO3. When it is mutated, old mice develop locomotor disorders and their mitochondria are abnormal. “We are now trying to find out if an overexpression of this gene in mice has the same neuroprotective effect as in flies. Concerning humans, we are testing this hypothesis using induced pluripotent stem cells: skin cells reprogrammed to give stem cells, then dopamine neurons. This is the next key step,” says the researcher.

Towards a new treatment?

If research confirms that the discovered gene also protects neurons in humans, this could pave the way for a new treatment for Parkinson’s disease. « We hope that this gene can be used to prevent or slow down the development of the disease, » says Emi Nagoshi. But above all, we still need to study the basic mechanisms and in particular find early markers of the disease. It will take time.”

For Professor Pierre Burkhard, assistant physician at the Neurology Department of the University Hospitals of Geneva (HUG), not involved in this research, « the study is interesting, because it brings a new candidate to the molecules that we know in Parkinson’s disease. . However, we cannot say that this gene will protect neurons, because we do not know if it is involved in the disease in humans. To date, existing drugs can only treat the symptoms. Most work by increasing the amount of dopamine in the brain, a neurotransmitter involved in movement that is lacking in disease. But after a few years, these treatments are less effective and it is necessary to deliver them via pumps which ensure a stable and constant supply. “When this is again insufficient, the last possible treatment is deep brain stimulation: the brain is operated on to implant a neurostimulator and electrodes, which restores motor skills,” explains the doctor.

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Published in Le Matin Dimanche on 08/05/2022.