Hope for Parkinson's Cure Rises as Stem Cell Therapy Restores Dopamine

Hope for Parkinsonís Cure Rises as Stem Cell Therapy Restores Dopamine

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Highlights:
  • 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.
Hope for Parkinsonís Cure Rises as Stem Cell Therapy Restores Dopamine

What is 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.

Symptoms:
  • Tremors or involuntary shaking
  • Delayed or slowed movement
  • Rigid muscles and stiffness
  • Loss of automatic movements including blinking

What did the latest study find?

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 producing neurons.

The 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?

Pluripotent stem 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.

Induced 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 ethical dilemma.

Important aspects of the study:

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 received.

Researcher 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 trials?

"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 degeneration.

What about rejection of the donor cells by the patient?

In another accompanying paper published in Nature Communications, Takahashi's 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.

Reference:
  1. 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

Source: Medindia

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