Stemming The Symptoms of Parkinson's
A recent study found that neurons taken from reprogrammed adult skin cells "took" when implanted into the brains of mice, and reduced Parkinson's symptoms in a rat with the disease. "This is the first demonstration that reprogrammed cells can integrate into the neural system or positively affect neurodegenerative disease," says lead author of the study, Marius Wernig, a researcher in Whitehead Member Rudolf Jaenisch's lab.
An earlier study from the Jaenisch lab which took place in 2007 showed that mice with the same human disease trait that causes sickle-cell anemia could be cured with adult skin cells that had been reprogrammed to resemble the embryonic stem cell state. In these neural experiments, Wernig employed induced pluripotent stem cells (IPS cells). These are created by retraining the adult skin cells through the use of retroviruses, which cause the expression of four genes inside the DNA of the cells: Oct4, Sox2, c-Myc and Klf4. After being reprogrammed, the IPS cells were changed into neural precursor cells and dopamine neurons, through the use of techniques that had been developed in embryonic stem cells at an earlier stage.
One experiment found Wernig transplanting neural precursor cells into the brain cavities of mouse embryos. Nine weeks later, it was evident that the implanted cells had clustered and then infiltrated brain tissues in the area. Through the use of electrophysiological studies made by MIT's Martha Constantine-Paton of the McGovern Institute for Brain Research and structural analysis, Wernig discovered that the migrating neural precursor cells had differentiated into many different subtypes of neural cells, such as neurons and glia. These had become integrated with the brain.
In an effort to evaluate the possible medical benefits of this discovery, the Jaenisch group worked with Ole Isacson's team at Harvard Medical School's Mclean Hospital, using a rat model with Parkinson's disease. Parkinson's is due to the lack of the hormone dopamine in a specific area of the midbrain. In order to create this state in rats, the neurons responsible for dopamine production were destroyed on one side of the rats' brains. Researchers then took cells differentiated into dopamine neurons and grafted these onto the brain part known as the striatum.
Four weeks post-surgery, the rats underwent testing to see if their behavior had been affected by the implanted dopamine neurons. When given amphetamine injections, rats tend to walk in circles moving in the direction of the side of the brain with the least dopamine activity. Of the rats which received the dopamine neuron transplants, 8 out of 9 circled less and some did no circling at all. After eight weeks, it was possible to see that the dopamine neurons had integrated into the surrounding brain tissues, as well.
"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."
Wernig and Jaenisch feel hopeful that their work may someday be used to help human patients, though there are many issues that need to be addressed before this can happen. For instance, the retroviruses used in reprogramming the cells have the potential of causing cancer and a way must be found to avoid this problem. In addition, methods must be developed for transplanting neural precursor cells into humans for the best effect.