A few mice with a tremor-inducing genetic condition seem to have been almost cured by a transplant of human fetal cells, according to research published in Cell Stem Cell1. Steve Goldman, a neuroscientist at the University of Rochester Medical Center in New York, who led the study, believes it is the first time human cell therapy has rescued a genetic brain disorder. Neurons in so-called 'shiverer' mice do not develop robust protective myelin sheaths; the mice suffer extreme involuntary shaking and die before they are five months old. To try to compensate for this defect, Goldman and his colleagues obtained human glial progenitor cells from aborted fetuses and transplanted them into shiverer mice that lacked functioning immune systems, a trait that enabled them to accept the human cells.

The researchers transplanted 26 newborn mice with 300,000 human cells, inserting them into five sites across the brain. A control set of 59 mice received no treatment, and a second control group of 29 mice received sham injections containing no cells. All the mice developed the shiverer symptoms; seizures were observed by six weeks; by 19 weeks, the mice's hindlimbs were so weak they could hardly walk. By the end of 23 weeks, all of the control mice and 20 of the 26 treated mice were dead.

The mice that survived, however, regained the ability to walk and stopped getting seizures. Four appeared cured and survived for over a year before they were killed so that their brains could be studied. These autopsies showed that while the neurons themselves were all mouse cells, at least a third of the myelinating cells were human. And these human glial cells myelinated just as many axons as were myelinated in wild-type controls.

Previous transplants of glial progenitor cells had little functional benefit, says Goldman. He thinks this attempt worked because of three improvements: a better way of collecting and purifying the glial progenitor cells; injecting the cells in such a way that more cells were better distributed about the brain; and a better way of preventing rejection of the transplanted cells. The shiverer mouse model could be relevant to a variety of myelin-related brain maladies, including cerebral palsy and Pelizaeus-Merzbacher disease.

Evan Snyder, a neuroscientist at the Burnham Institute in San Diego, California, who has published similar results with mouse cells2, calls the results “very encouraging,” particularly the extensive levels of engraftment. He notes, however, that it's unclear how the shiverer model relates to human disease, and that overcoming immune rejection could be tricky.

Goldman says his next step is to better define why the treatment works for a few treated mice but not others, and to use that understanding to make the treatment more effective. He says he's optimistic about one day using such a strategy for human disorders and is currently collaborating with Ian Duncan at the University of Wisconsin in Madison to transplant cells to dogs with a genetic myelin disorder to better understand how the cells disperse in larger animals.