Parkinson's stem cell therapy works in rats

Dopamine-making neurons derived from human embryonic stem cells. — Jeannie Liu in the lab of Jan Nolta at the University of California, Davis.ENTS

By Bradley J. Fikes10:04 A.M.NOV. 9, 2014
A rat model of Parkinson's disease has been successfully treated with neurons derived from human embryonic stem cells, according to a study led by Swedish scientists. It’s a promising sign for scientists at The Scripps Research Institute and Scripps Health who hope to perform similar therapy on Parkinson’s patients, using artificial embryonic stem cells.

In rats and people, neurons that make the neurotransmitter dopamine are essential for normal movement. The cells are destroyed in Parkinson's, leading to the difficulty in movement that characterizes the disease.

Researchers transplanted dopamine-producing cells grown from human embryonic stem cells into the brains of rats whose own dopamine-making neurons had been destroyed. The rats were immune-suppressed so they would not reject the cells. Within five months, the transplanted cells boosted dopamine production to normal levels, restoring normal movement in the rats.

The study was published Thursday in the journal Cell Stem Cell. The senior author was Malin Parmar of Lund University in Lund, Sweden.

Parkinson's embryonic stem cell therapy

The results support the Scripps approach of using the artificial embryonic stem cells, called induced pluripotent stem cells, said Jeanne Loring, who heads the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla. Loring is part of a group called Summit 4 Stem Cell that's raising funds to treat eight Parkinson's patients with their own IPS cells.

Particularly significant is the study's comparison of the effects of dopamine-making neurons derived from fetal cells to that of embryonic stem cells, Loring said by email.

"In the 1980s and 1990s, there were several clinical trials that showed that grafts of fetal brain containing the precursors of dopamine neurons could reverse the effects of Parkinson's disease in some patients," Loring said. "We, and the others developing stem cell therapies, based our plans on the results of those studies, but no one had ever directly compared fetal tissue and human pluripotent stem cell-derived dopamine neurons in an animal model of PD."

Induced pluripotent stem cells appear to have much the same capacity as human embryonic stem cells to generate different tissues and organs.

There has been uncertainty about how similar they are to each other, specifically whether the IPS process produces mutations. But recent studies have found the cell types are extremely similar, including a study also published in Cell Stem Cell on Thursday. That study compared IPS cells with embryonic stem cells produced by SCNT, or somatic cell nuclear transfer, the same process used to create Dolly the sheep.

Evan Snyder, a stem cell scientist at the Sanford-Burnham Medical Research Institute in La Jolla, said by email that the work is well-done, but represents an "incremental advance."

"From what I see so far, the work is done in a very meticulous fashion and answers the question of whether hESCs (human embryonic stem cells) can give rise to neurons that worked as well as the old fetal tissue used to do," Snyder said. "However, unless you are a PD maven, it really is just an incremental advance.

"The techniques are not new. the method for making the cells has been out there for a while,' he said. "The model is only a rat, not a monkey. So there would need to be a lot of work before going into humans -- like whole monkey studies, as we are doing."

• Snyder is researching Parkinson's treatment derived from another type of stem cell, grown from parthenogenetic, or unfertilized human egg cells. The research is being performed in monkeys, which have a nervous system more similar to humans than do rats. International Stem Cell, based in Carlsbad, plans to commercialize the therapy if successful.

  Both the parthenogenetic and induced pluripotent methods have advantages and drawbacks. Induced pluripotent stem cells can be created from the patient's own cells, typically skin cells. This minimizes the chance of immune rejection. However, such a patient-customized therapy incurs additional expenses over a therapy made for many patients. The parthenogenetic stem cells are immune-matched to large numbers of patients, but rejection is still a possibility.

  The complete study is available at: utsandiego.com/parkesc.

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