Researchers affirm
long-held belief that viruses can trigger Parkinson’s disease
By Ann Kellett, PhD
An infectious model more accurately
shows how the disease might emerge and progress over time
Parkinson's disease is second only to dementia among brain
disorders. Scientists
usually use animal models when studying Parkinson’s disease because these models mimic the
disease well. They are limited, however, because they require either gene
modifications or the injection of toxicants, which may not accurately represent
how the disease occurs in humans.
But now, researchers at Texas A&M University have
developed a model that uses a nontoxic way to generate the symptoms of
Parkinson’s: infection with a virus called Theiler’s murine encephalomyelitis virus (TMEV),
a natural pathogen in mice.
Their study is
a game changer because it proves that a simple viral infection can trigger the
exact brain damage and physical disabilities in animal models that are seen in
people with Parkinson’s disease—and it sets the stage for additional studies.
“The toxic-exposure models are useful for studying
Parkinson’s, but not all people who are exposed to chemicals go on to develop
Parkinson’s, so these models cannot show all the ways a disease as complex as
Parkinson’s actually begins or develops over time in people,” said Candice Brinkmeyer-Langford,
PhD, a neurogenerative disease expert with the Texas A&M
University School of Public Health at Texas A&M Health.
Parkinson’s affects more than 10 million people worldwide,
making it second only to dementia among brain disorders. It destroys the cells
that produce dopamine, a chemical essential for smooth body movement, leading
to problems with balance and walking, tremors in the hands or fingers and
overall stiffness, as well as mental or emotional distress.
Its origins are unknown, but for decades, experts have
believed that the disease could be triggered by the brain inflammation caused
by viruses—even those contracted decades earlier—as well as by a combination of
a person’s genetics and environmental factors. This idea recently was affirmed by Brinkmeyer-Langford and
others at Texas A&M in the case of another
devastating motor neuron disease, amyotrophic lateral sclerosis (ALS).
“Viruses are known to cause entirely different diseases
based on a person’s genetics,” she said. “For example, the Epstein-Barr
virus causes mononucleosis, but may also contribute to cancer or multiple
sclerosis, and SARS-CoV-2 can attack the heart and brain as well as the
lungs.”
For this pilot study to test the validity of TMEV in
studying Parkinson’s, the researchers conducted experiments to measure the
following:
·
Brain cell infection and damage. One
week after infection, the researchers confirmed that the virus had infected the
dopamine-producing brain cells. At one month after infection, the
dopamine-producing cells were destroyed in the site of viral infection.
Dopamine-induced behaviors were compared between 13 infected animal models and
14 healthy control animal models after administering a dopamine-mimicking drug which produced
a distinct movement pattern confirming dopamine neuron loss. This test
confirmed that the virus caused a significant loss of these crucial dopamine
brain cells over time.
·
Speed and coordination. They
compared 13 infected animal models against 14 healthy control animal models to
track and measure their motor skills with a standard assessment called
the pole test to determine if losing
dopamine-producing cells causes the physical movement problems typically seen
in Parkinson’s patients. Animal models infected with TMEV had slower times to
complete the test compared to the healthy control models, and this still was
the case at week 20, when the study ended.
·
Gait abnormalities. They
used a specialized treadmill, which evaluated over 100 factors involved in
walking, motor function and balance, to analyze how quickly and efficiently the
animal models walked. The test confirmed that the virus caused physical
weakness following the loss of dopamine producing cells due to viral infection,
proving that the virus damaged the brain in a similar way as seen in
Parkinson’s patients.
Now that this innovative model has been proven,
Brinkmeyer-Langford said future studies will include testing the TMEV model
directly against standard, older animal models used in Parkinson’s research,
looking for early warning signs and biological markers for Parkinson’s and
analyzing how the body’s immune response to a virus changes the brain.
“The clock is ticking, since the rapidly aging global
population means the number of people with Parkinson’s is expected to jump significantly,” she said.