Treatment for Parkinson's could now get even better

Date:
February 18, 2022
Source:
University of Copenhagen - The Faculty of Health and Medical
Sciences
Summary:
Specialized groups of neurons within the brainstem control
movement. Now researchers have found that activation of such
neurons is sufficient to restore full movement function in mice with
symptoms of Parkinson's Disease. The study helps clinicians to focus
Deep Brain Stimulation to the right therapeutic spot and hopefully
could improve treatment of motor symptoms in Parkinson's Disease.



FULL STORY ========================================================================== Specialized groups of neurons within the brainstem control movement. Now researchers have found that activation of such neurons is sufficient
to restore full movement function in mice with symptoms of Parkinson's
Disease. The study helps clinicians to focus Deep Brain Stimulation
to the right therapeutic spot and hopefully could improve treatment of
motor symptoms in Parkinson's Disease.


========================================================================== Parkinson's is a neurodegenerative disease where dopaminergic neurons progressively die in the brainstem. Tremor and difficulties to walk
are recognizable movement symptoms for many people suffering from
Parkinson's. Over time, nearly a quarter of patients will have so much
trouble walking that they often end up freezing on the spot and falling,
and many become housebound.

People are primarily treated with medicine, but in some cases doctors use
Deep Brain Stimulation (DBS). In DBS, the surgeon places a thin metal
wire in the brain, which can be used to send electrical pulses. DBS is effective in treating tremor, but alleviating difficulties in walking
and freezing remains a challenge.

Now, a study from the University of Copenhagen conducted in mice
demonstrate that DBS treatment of walking problems in Parkinson's could
be optimised by targeting specific eurons in the brainstem -- possibly benefitting some of the more than 7 to 10 million people suffering from
the disease worldwide.

"Brainstem DBS are the right strategy to facilitate patients to walk
properly again" Based on previous animal studies of motor circuits, which
are responsible for the planning, control, and execution of voluntary movements, scientists has hypothesized that freezing of walking in
Parkinson's could be alleviated. That would require DBS to stimulate
neurons in the pedunculopontine nucleus (PPN), which is located in the brainstem. The PPN was thought to send signals from the brain to the
spinal cord leading to body movements.



========================================================================== "However, initial results from clinical trials with DBS of the PPN had
very variable effect on movement recovery, particularly in patients
who experience freezing of walking. It has therefore been debated where
within the brainstem an optimal stimulation should be. Our study brings
new knowledge to the table regarding the best area for DBS in order to alleviate this particular symptom," says corresponding author Professor
Ole Kiehn at the Department of Neuroscience.

Previous results from the group showed that stimulation of so-called
excitatory neurons in the PPN could initiate locomotion in normal mice. It raised the possibility that these nerve cells could indeed be used to
treat movement symptoms in mice with features of Parkinson's Disease.

"We use a technology to target specific group of cells in the PPN in
order to close in on what areas are the best to stimulate, if we want
to alleviate these particular symptoms. The result shows that the motor improvement is optimal, if we stimulate what we call excitatory neurons
in the caudal area of the PPN," explains Ole Kiehn.

"We believe that clinical trials with brainstem DBS are the right strategy
to facilitate patients to walk properly again. But the variable clinical results occur, because DBS would require higher precision to target the particular group of neurons in the caudal PPN. It is a very delicate
area, because if we were to stimulate excitatory neurons in other areas
than the caudal PPN, it would cause complete immobilization instead."
The key is the activation of PPN neurons In Parkinson's Disease, nerve
cells that produce dopamine progressively die.

Since the 1960s, doctors have relied on medication to replace the missing dopamine, but it is notoriously difficult to fully control symptoms as
the disease progresses.



==========================================================================
"In many people the movement symptoms do not respond well to medical
treatment in the later stages of this disease, so there has been done
a lot of research into alternative treatments, including a search for
optimal targets for deep brain stimulation," explains Postdoc Debora
Masini, first author of the new study, which included several different strategies to substantiate their findings.

"When we stimulated these specific neurons in the caudal area of the PPN,
the animals were able to walk normally, across longer distances and with
normal walking speed, as opposed to before the stimulation, where they
would display symptoms of Parkinson's Disease," says Debora Masini.

"We systematically compared stimulation of different locations and cell
types in a series of complementary experiments. And they all pointed
towards the same conclusion. It strongly indicates these excitatory
neurons in the caudal PPN are an ideal target for recovery of movement
loss," she says.

The researchers hope that the new study could aid clinicians when they
pick the exact location for DBS in the brainstem.

"The mice in our study only partially represents the complexity of this disease, but the results have been very telling. Nearly everything
we have learned in the beginning on how to treat Parkinson's Disease
comes from animal models, including the medication we use nowadays for patients. In this sense, it is a valid approach, and we hope our study
can help provide better treatment for human patients," says Debora Masini.

special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by University_of_Copenhagen_-_The_Faculty_of_Health_and
Medical_Sciences. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. De'bora Masini, Ole Kiehn. Targeted activation of midbrain neurons
restores locomotor function in mouse models of parkinsonism. Nature
Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-28075-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220218100701.htm

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