Reprogrammed adult skin cells treat Parkinson’s disease in animal model

3 min read

Study raises prospect of eventual human treatment

Researchers at the Whitehead Institute and Harvard Stem Cell Institute(HSCI) have reported successfully reducing symptoms in a Parkinson’s disease rat model by using dopamine producing neurons derived from reprogrammed adult skin cells(iPS).

The work was reported in a study published in the online Early Edition of Proceedings of the National Academy of Science.

“This is the first demonstration that reprogrammed cells can integrate into the neural system or positively affect neurodegenerative disease,” said Marius Wernig, lead author of the article and a postdoctoral researcher in Whitehead Member Rudolf Jaenisch’s lab.

Ole Isacson, a Harvard Stem Cell Institute Principal Faculty Member, whose laboratory is at McLean Hospital, and colleagues used green fluorescent protein to mark the cells that had become dopamine-making neurons, so that only these desired cells were transplanted into the rat brains.

“We have just started now to work on the human equivalents,” Isacson told Reuters.

Rudolph Jaenisch, the senior author on the paper, said that the “experiment shows that in vitro reprogrammed cells can in principle be used to treat Parkinson’s disease.”

Wernig used a rat model for Parkinson’s disease, a human condition caused by insufficient levels of the hormone dopamine in a specific part of the midbrain. To mimic this state, the dopamine-producing neurons were killed on one side of the rat brains. In collaboration with Ole Isacson’s HSCI group at McLean Hospital, Wernig then grafted differentiated dopamine neurons into a part of the rat brains called the striatum.

Four weeks after surgery, the rats were tested for dopamine-related behavior. In response to amphetamine injections, rats typically walk in circles toward the side with less dopamine activity in the brain. Eight of nine rats that received the dopamine neuron transplants showed markedly less or even no circling. Eight weeks after transplantation, Wernig could see that the dopamine neurons had extended into the surrounding brain.

“This experiment shows that in vitro reprogrammed cells can in principle be used to treat Parkinson’s disease,” says Jaenisch. “It’s a proof of principle experiment that argues, yes, these cells may have the therapeutic promise that people ascribe to them.”

The researchers are optimistic that this work eventually could be applied to human patients, but caution that major hurdles must be addressed first. Those include finding alternatives to the potentially cancer-causing retroviruses used to transform the skin cells into IPS cells and figuring out the best methods and places to transplant the neural precursor cells in humans.

The research was supported by the Ellison Medical Foundation and the National Institutes of Health.