- Parkinson's disease is a motor
disorder characterized by uncontrolled movements due to lack of a
neurotransmitter called dopamine.
- Donor-matched human stem cells
restored dopamine in monkeys that were modified to model the disease and
enabled them to move around in the cage.
- Scientists say that after success
in monkeys, human trials are likely to begin by the end of 2018.
Parkinson's disease is a neurodegenerative disease,
where dopamine producing neurons in the brain are lost. Since dopamine is a
neurotransmitter that controls body movement, patients with Parkinson's have
limited movement and stiffness of muscles. Current treatment is only aimed at
treating the symptoms of the disease and not the underlying cause. A team of
researchers at the Center for iPS Cell Research and Application, Kyoto
University, Japan, have reported success in restoring dopamine using induced
pluripotent stem cells (iPSC) in monkeys. The research is published in Nature
Parkinson's disease and its symptoms?
Parkinson's is a progressive disorder that worsens with
time. It is a disorder of the nervous system that affects movement. In
Parkinson's the neurons that produce a chemical messenger called dopamine
is destroyed. Since
dopamine is responsible for the control of body movements, a majority of
parkinsonian symptoms restrict movement. While the exact cause of the disease
remains unknown, genetic and environmental factors are believed to play a role
in disease development and progression.
‘Induced pluripotent stem cells from matched donors were able to restore dopamine in Parkinsonís disease simulated monkeys.’
What did the
latest study find?
- Tremors or
- Delayed or
- Rigid muscles
- Loss of
automatic movements including blinking
Takahashi's team transformed adult
stem cells from both healthy people and those with Parkinson's into
dopamine-producing neurons. These are called induced pluripotent stem cells
(iPSC). These were then transplanted into macaque†monkeys which were
earlier modified to model Parkinson's disease
by killing the dopamine
monkeys showed significant improvement in their symptoms two years after having
dopamine producing neurons derived from human stem cells transplanted into
their brains. It was also observed that the monkeys began moving around their
cages more frequently.
What are iPSC and why were they used?
cells (PSC) are undifferentiated cells that can form any cell type of the body.
That is, this one cell can form heart cells, hair cells, brain cells (neurons)
and many more. Researchers have long proposed the idea of using PSCs to replace
the dead dopamine-producing neurons in people with Parkinson's. This could
potentially halt or even reverse disease progression. But the source of these pluripotent stem cells
are human embryos and that has
been a subject of ethical debate.
pluripotent stem cells (iPSC), on the
other hand are ordinary adult cells that are genetically treated in
laboratories to behave like embryonic pluripotent stem cells. These can be made
to differentiate into dopamine producing neurons and also do not involve an
Important aspects of the
Development of tumors and a
heightened immune response is a common phenomenon associated with experimental
stem cell therapies. However, brain scans of the stem cell transplanted monkeys
showed that the cells were functioning as expected and no damaging immune
response or growth of cancers was observed.
The researchers also found that
the quality of the donor cells was the key factor and not how many each monkey
Prof Jun Takahashi, from Kyoto University, said "The work, published in the
journal Nature, showed that the artificially created cells were as effective as
those created naturally in the brain of the monkeys."
When can we expect clinical
"I hope we can begin a clinical trial by the
end of next year," says Takahashi. Such a trial would be the first iPS cell
trial for Parkinson's. In 2014, a Japanese woman in her 70s became the first
person to receive cells derived from iPS cells, to treat her macular
What about rejection
of the donor cells by the patient?
In another accompanying paper
published in Nature Communications,
team found that when transplant was done between monkeys carrying similar white
blood cell markers, the immune response in the patient was much lower and could
be controlled by immunosuppressants.
- Tetsuhiro Kikuchi, Asuka Morizane, Daisuke Doi, Hiroaki Magotani, Hirotaka Onoe, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Ryosuke Takahashi, Haruhisa Inoue, Satoshi Morita, Michio Yamamoto, Keisuke Okita, Masato Nakagawa, Malin Parmar, Jun Takahashi. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model. Nature, 2017; 548 (7669): 592 DOI: 10.1038/nature23664