iPS Cell-based Neuron Therapy Benefits Monkeys With Parkinson’s – ReliaWire

By JoanneRUSSELL25

Monkeys with Parkinsons disease symptoms show significant improvement over two years after being transplanted neurons prepared from human induced pluropontent stem cells, scientists at the Center for iPS Cell Research and Application (CiRA), Kyoto University, report. One of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys.

Parkinsons disease degenerates a specific type of cells in the brain known as dopaminergic (DA) neurons. It has been reported that when symptoms are first detected, a patient will have already lost more than half of his or her DA neurons.

Several studies have shown the transplantation of DA neurons made from fetal cells can mitigate the disease.

The use of fetal tissues is controversial, however. On the other hand, iPS cells can be made from blood or skin.

Our research has shown that DA neurons made from iPS cells are just as good as DA neurons made from fetal midbrain. Because iPS cells are easy to obtain, we can standardize them to only use the best iPS cells for therapy,

said Professor Jun Takahashi, a neurosurgeon specializing in Parkinsons disease, who plans to use DA neurons made from iPS cells to treat patients.

To test the safety and effectiveness of DA neurons made from human iPS cells, Tetsuhiro Kikuchi, a neurosurgeon working in the Takahashi lab, transplanted the cells into the brains of monkeys.

We made DA neurons from different iPS cells lines. Some were made with iPS cells from healthy donors. Others were made from Parkinsons disease patients,

said Kikuchi, who added that the differentiation method used to convert iPS cells into neurons is suitable for clinical trials.

It is generally assumed that the outcome of a cell therapy will depend on the number of transplanted cells that survive, but Kikuchi found this was not the case. More important than the number of cells was the quality of the cells.

Each animal received cells prepared from a different iPS cell donor. We found the quality of donor cells had a large effect on the DA neuron survival, Kikuchi said.

To understand why, he looked for genes that showed different expression levels, finding 11 genes that could mark the quality of the progenitors. One of those genes was Dlk1.

Dlk1 is one of the predictive markers of cell quality for DA neurons made from embryonic stem cells and transplanted into rat. We found Dlk1 in DA neurons transplanted into monkey. We are investigating Dlk1 to evaluate the quality of the cells for clinical applications.

Another feature of the study that is expected to extend to clinical study is the method used to evaluate cell survival in the host brains. The study demonstrated that magnetic resonance imaging (MRI) and position electron tomography (PET) are options for evaluating the patient post surgery.

MRI and PET are non-invasive imaging modalities. Following cell transplantation, we must regularly observe the patient. A non-invasive method is preferred,

said Takahashi.

The group is hopeful that it can begin recruiting patients for this iPS cell-based therapy before the end of next year. The study is the teams answer to bring iPS cells to clinical settings, said Takahashi.

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 TakahashiHuman iPS cell-derived dopaminergic neurons function in a primate Parkinsons disease modelNature, 2017; 548 (7669): 592 DOI: 10.1038/nature23664

Image: Annie Cavanagh / Wellcome Images

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iPS Cell-based Neuron Therapy Benefits Monkeys With Parkinson’s – ReliaWire

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