Scientists have found that a technique for targeting a specific group of brain cells associated with Parkinson’s disease is also effective at treating a separate group of brain cells.

Researchers may have found a new two-pronged treatment approach to Parkinson’s disease.
These findings now appear in the journal Neurotherapeutics.

The initial technique is a type of gene therapy that researchers first used to target cholinergic neurons in the brains of rats in 2015. Cholinergic neurons are a type of nerve cell that Parkinson’s affects.

Now, by using brain imaging techniques, the scientists have discovered that their method also positively affected a group of cells near the cholinergic neurons, called dopaminergic neurons.

About Parkinson’s disease
According to the National Institute of Neurological Disorders and Stroke, Parkinson’s disease is a type of neurological condition that typically affects people over the age of 60.

Symptoms include tremors or tremblings, rigidity or stiffness in the trunk or limbs, slowness of movement, and impaired balance.

These symptoms occur because the condition causes a reduction in a person’s dopamine-producing brain cells, or the dopaminergic neurons.

Cell-to-cell interaction
The original method, which the researchers showcased in 2015, worked by using a virus to deliver a genetic modification to the cholinergic neurons of rats genetically modified to develop Parkinson’s disease. The scientists then used a drug that could stimulate the targeted neurons.

In the new study, the scientists showed how they used brain imaging technology to reveal a clear channel of communication between the cholinergic neurons, which they targeted in the 2015 study, and the nearby dopaminergic neurons.

Through cell-to-cell interaction, stimulating the rats’ cholinergic neurons also stimulated their dopaminergic neurons. This seemed to restore the dopamine-producing function in the dopaminergic neurons.

As a result of this, the rats made a complete recovery, including movement restoration and a reversal of postural impairment.

According to senior study author Dr. Ilse Pienaar, “When we used brain imaging, we found that as we activated cholinergic neurons, they then interacted directly with dopaminergic neurons.”

“This seems to be a knock-on effect, so by targeting this one set of neurons, we now know that we are able to also stimulate dopaminergic neurons, effectively restarting the production of dopamine and reducing symptoms,” she adds.

“This is really important, as it reveals more about how nerve systems in the brain interact, but also that we can successfully target two major systems […] affected by Parkinson’s disease, in a more precise manner.”

– Dr. Ilse Pienaar

A future treatment for Parkinson’s?
This means that, in the future, researchers may be able to develop a more effective and less invasive treatment for Parkinson’s disease in humans.

Current Parkinson’s treatments focus on managing the condition by using drugs, but these often have significant side effects, and they typically become ineffective after 5 years.

Alternative treatments include deep brain stimulation, which is an invasive procedure that releases electronic pulses in a person’s brain. However, the results from this procedure are mixed, which researchers believe is because it affects all cells in a person’s brain, rather than only the specific cells that Parkinson’s affects.

What makes the new findings promising is the fact that the treatment is both noninvasive and targeted, producing excellent results in rats.

As Dr. Pienaar explains, “For the highest chance of recovery, treatments need to be focused and targeted but that requires a lot more research and understanding of exactly how Parkinson’s operates and how our nerve systems work.”

“Discovering that both cholinergic and dopaminergic neurons can be successfully targeted together is a big step forward.”

– Dr. Ilse Pienaar

“While this sort of gene therapy still needs to be tested on humans, our work can provide a solid platform for future bioengineering projects.”

Study co-author Lisa Wells adds: “It has been an exciting journey working with Dr. Pienaar’s team to combine the two technologies to offer us a powerful molecular approach to modify neuronal signaling and measure neurotransmitter release. We can support the clinical translation of this ‘molecular switch’ into clinical utility through live imaging technology.”