05 March 2015

Dopamine neurons from fibroblasts have taken root in the monkey's brain

Neuron transplantation "from a test tube" can cure Parkinson's disease

Anna Govorova, Infox.ru

Bioengineers from the Stem Cell Institute at Harvard University have managed to make significant progress in the development of treatments for Parkinson's disease, Infox reports.

The authors have grown dopamine-releasing neurons from the skin cells of monkeys with this disease, which are destroyed in Parkinson's disease. Then, for the first time, these neurons were implanted into the animal's brain, where they took root and worked perfectly. The symptoms of the disease in the monkey disappeared after transplantation of such neurons.

According to the authors, they hope that in the near future they will be able to start the first stage of clinical trials of this method. However, this may not happen earlier than in three years.

Parkinson's disease is a severe neurodegenerative disease. It occurs due to the destruction of nerve cells in the brain that synthesize dopamine. Dopamine is the most important neurotransmitter, that is, an intermediary in the transmission of a nerve impulse from neuron to neuron. The main symptoms of Parkinsonism are difficulty in movement, impaired coordination, muscle rigidity, tremor, mental disorders, cognitive impairment. Currently, therapy can only reduce the symptoms of the disease. This is done with the help of medications, and in rare cases, embryonic stem cell transplantation is performed.

In 2011, bioengineers from the San Rafael Institute (Italy) for the first time managed to obtain dopamine-releasing neurons "in vitro" from human skin cells. Then the authors used direct reprogramming, bypassing the stem cell stage. Scientists hoped that in the future, growing such neurons from the skin of patients with Parkinson's disease, and then implanting them in the brain, would become one of the methods of treating this disease. However, in that experiment, the authors did not transplant the resulting neurons.

In the current study, Dr. Ole Isacson and his colleagues used fibroblasts – skin cells of a monkey with Parkinson's disease. Scientists have been working on setting up the experiment for more than 15 years. Initially, they turned skin cells into induced pluripotent stem cells, which have the ability to transform into almost any cells and tissues. Then they treated these cells with certain growth factor proteins, turning them into dopamine–releasing neurons.


Neurons that bioengineers have grown.
A snapshot from the article Possible progress against Parkinson's (B.D.Colen, Harvard Gazette) – VM.

The next stage of the experiment was the transplantation of these neurons into the monkey's brain.

Two years after implantation, as scientists found out, these cells continued to work, and the animal's symptoms of Parkinson's disease noticeably decreased.

Moreover, as the authors add, the monkey did not receive immunosuppressive therapy, since related cells obtained from its own fibroblasts were transplanted.

"For the first time, we were able to conduct a similar experiment with the transplantation of dopamine-releasing neurons derived from fibroblasts. And for the first time such a transplant led to success – the symptoms of Parkinson's disease in the animal disappeared. The monkey moved around the enclosure in the same way and with the same agility as healthy animals," says Isakson.

According to scientists, they are now working on creating a protocol to proceed to the first stage of clinical trials of this method. However, such preparation will take a long time: the tests should begin no earlier than in three years.

The article by Ole Isakson and his colleagues was published in the latest issue of the journal Cell Stem Cell (Hallett et al., Successful Function of Autologous iPSC-Derived Dopamine Neurons following Transplantation in a Non-Human Primate Model of Parkinson's Disease).

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