Stem Cells Could Provide New Hope for Parkinson’s Patients

From an ordinary skin cell to a brain cell: When researchers announced that they could turn a skin cell into a stem cell by "reprogramming," it opened the possibility that stem cell therapies might avoid the ethical hurdles of obtaining such cells from embryos.

These "reprogrammed" stem cells, also called induced pluripotent stem (iPS) cells, seem to have the ability to transform into any kind of cell (a property known as pluripotency). The iPS cells can then be grown in culture until they become fully differentiated neurons. The neurons can be used to replace dopamine-producing cells, the type of brain cells damaged in Parkinson's disease.

Parkinson's disease is a slowly progressing, degenerative disease that affects the central nervous system (affecting motor skills and speech). It is a chronic disease that persists over a long period of time, and the symptoms grow worse over time. Although the disease may appear in younger patients (even teenagers), it usually affects people in late middle age, and affects men and women in almost equal numbers. It is not contagious, nor is there any hard proof that it is passed on genetically.

The latest discoveries involving iPS cells were conducted by a research team, led by Rudolph Jaenisch at the Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology (MIT). The team used a previously developed method for "reprogramming" cells, (infecting the skin cells of mice with a retrovirus carrying four genes), which gave the cells pluripotent properties. Once the skin cells were turned into functioning neurons in the culture, they were transplanted into the brains of mice while they were still fetuses. When the mice reached adulthood researchers examined the brains and found that the cells had migrated and matured nicely into the brain, adopting functions of mature neurons.

The researchers then wanted to know if these functioning neurons could repair a defect in a diseased animal. The study created a model for Parkinson's in which rats were given a toxin to kill the dopamine neurons on one side of the brain. While the rats appeared normal, when their dopamine neurons were stimulated with amphetamine, the rats ran in circles in the direction of the damaged side. Their motor defect improved when they were given transplanted neurons derived form iPS cells.

It is not known exactly how such a powerful state can be achieved by boosting the expression of just four genes. Two of the genes are tumor promoters known as oncogenes, which help the cells proliferate, and the other two work in maintaining the pluripotency of the stem cells.

Similar experiments have been performed in animals using stem cells from embryos or created with nuclear transfer, also known as therapeutic cloning. However, iPS cells offer a way to avoid the ethical question of embryo use as well as the technical challenges of nuclear transfer. And the potential complications caused by immune rejection of foreign tissue would be non-existent as the cells came from the patient's own skin.

Although the study shows the concept holds promise, there is much research left to do before the "reprogrammed" stem cells could be used on any of the 50,000 Americans diagnosed with Parkinson's disease each year. More people suffer from Parkinson's disease than multiple sclerosis, muscular dystrophy, and amyotrophic lateral sclerosis combined, with more than half a million Americans affected at any one time.