New Study Reveals Molecular Signs of Parkinson's Disease
Parkinson’s Disease is a widespread chronic
health issue that causes the degeneration of the central nervous
system, which severely affects motor functions over time in addition to
causing a number of other symptoms, including cognitive impairment,
depression, fatigue, and sleeping problems. This disease is
unfortunately fatal and causes a gradual degradation of the body and
mind, though most of the symptoms can be managed and staved off by
taking the right combination of medicine and possibly surgery.
While there is much information available
about the treatments and symptoms of this disease in both its early
stages and more advanced stages, the cause of Parkinson’s and it’s
molecular structure have only just begun to be understood in this recent
study.
The Development of Parkinson’s Disease
Parkinson’s Disease is identified by the
gradual degeneration of the central nervous system causing muscle
rigidity, slow movements, and imbalance. The development of this disease
is closely related to the production of neurons, neurotransmitters, and
hormones that play a major role in motor functions.
The main chemical produced by the brain that contributes to motor
function is dopamine, so when the nerve endings that produce dopamine
become impaired or die, the motor system suffers and steadily degrades.
Another set of neurotransmitters that become impaired in a person
suffering from Parkinson’s disease are the nerve-endings that produce
norepinephrine.
This particular chemical is one of the main messengers of the nervous
system, controlling automatic bodily functions like blood pressure,
heart rate, and digestion. It is largely the death and impairment of
these neurotransmitters that lead to various progressive symptoms of
Parkinson’s. However, the exact cause of neuronal failure remains
unknown.
Parkinson’s disease affects nearly 500,000
people, and those numbers are, sadly, on the rise. While 90% of patients
diagnosed are above the age of 60, the remaining 10% are within the
21-50 age bracket. It is these early cases that create the most worry,
and at the same time, they show the most potential for identifying the
molecular changes to the body that occur at the earliest stages of
Parkinson’s disease.
What the Study Revealed
The study, published on 27th January 2020
in the journal Nature Medicine, was focused on the symptoms and
development of the disease in young patients between the ages of 21 and
50. The study was conducted by a team of researchers from Cedars-Sinai
and UCLA, and it first began by harvesting and generating special stem
cells from young patients suffering from Parkinson’s. These stem cells
are called induced pluripotent stem cells (iPSCs for short), and they
are created by turning back the clock on adult cells by turning them
into primitive embryonic cells.
These embryonic cells, iPSCs, can then produce genetically identical
cells, replicating any type of cell in the human body. Using the iPSCs,
the dopamine neurons of early-onset Parkinson’s patients were
replicated, cultured in a dish, and analyzed. The goal, according to the
senior author of the study Dr.Clive Svendsen, was to take the cells
back to the earliest stages of their development and observe these
dopamine neurons in the earliest stages of the disease, prior to major
impairments.
Two major observations were detected. The
first was a build-up of a protein commonly found in forms of Parkinson’s
disease called alpha-synuclein in the neurons. The second observation
was the malfunctioning of a number of lysosomes. Lysosomes are tiny sacs
of enzymes in the cell that aid in digestion by acting as waste
disposal systems, or “trash can” organelles that break down and dispose
of proteins.
It could, therefore, be reasonably assumed that when the malfunctioning
of these lysosomes occurs, it results in the accumulation of the
alpha-synuclein protein in neuronal cells.
This technique and these observations show
the first signs of early-onset Parkinson’s, which would likely imply
that the build-up of alpha-synuclein over 2 or 3 decades could cause the
progression of the symptoms of the disease. The greater the
accumulation, the more severe the symptoms.
A Great Sign of Progress
These abnormalities are now being studied
to determine their presence in other forms of Parkinson’s disease. The
technique described in this study not only provided the team of
researchers a method that helps us understand the progression of the
disease on a molecular level, but also a means of drug testing.
The iPSCs were used to test a variety of drugs, one of which was found
to reduce the high levels of alpha-synuclein. This drug, PEP005, was
tested in both the dopamine neurons in the dish, as well as in lab mice,
and was found to reduce alpha-synuclein levels. The benefit of this
drug is that it has already been approved by the FDA (United States Food
and Drug Administration) as a treatment for precancerous tumors of the
skin.
An additional surprising result of using
the drug, PEP005, is an abnormal increase in the levels of an active
protein called kinase C. However, the relation of this protein to
Parkinson’s disease is still undiscovered. Experiments are being
conducted to determine how the drug PEP005 might be used to treat or
even prevent early-onset symptoms of Parkinson’s.
What Makes This Research So Important
Dr. Michele Tagliati, professor and
vice-chair of the Department of Neurology at Cedars-Sinai, director of
the Movement Disorders Program and a co-author of the study stated that
“Young-onset Parkinson's is especially heartbreaking because it strikes
people at the prime of life… This exciting new research provides hope
that one day, we may be able to detect and take early action to prevent
this disease in at-risk individuals."
This study shows great potential for the future of Parkinson’s disease
and in the discovery of possible preventive measures, treatments, and
cures. This joint effort between Cedars-Sinai and UCLA also marks an
important milestone in collective medical advancement.
As Dr. Shlomo Melmed of Cedars-Sinai said, “This research is an
outstanding example of how physicians and investigators from different
disciplines join forces to produce translational science with the
potential to help patients.” This study marks one of many incredible
collaborative programs from the past and hopefully for the future on
Parkinson’s Disease.