A newly discovered method for reprogramming human cells has enabled a team of scientists from the University at Buffalo to obtain a high yield of “designer dopamine neurons,” marking a considerable improvement on pre-existing techniques. While the implications of this research could be wide-reaching, initial reactions have focused on its potential to treat Parkinson’s disease.
The condition has long been associated with the gradual loss of dopamine neurons in a region of the brain called the substantia nigra. These cells are involved in the regulation of voluntary movement, yet are thought to degenerate at a rate of 5-10 percent per decade due to inflammation and oxidative stress, which occurs when parts of the cell accumulate damage from highly reactive molecules called reactive oxygen species (ROS). For this reason, scientists have sought an effective way to produce these so-called dopaminergic cells in the laboratory, yet had until now struggled to do so in sufficient numbers.
Publishing their findings in the journal Nature Communications, the team behind the discovery identified a particular protein called p53 as the major stumbling block. As a transcription factor, the role of p53 is to “read” the genetic information that determines the identity of a given cell, thereby acting as a “gatekeeper” that prevents the cell from being converted into something else. However, by interfering with the production of the p53 protein, the team was able to supress its activity, thus opening up the possibility of reprogramming cells.
Armed with this information, the researchers were able to convert human fibroblasts into induced dopaminergic (iDA) neurons. This involved first inhibiting p53 and then adding a cocktail of other molecules previously found to be crucial for the expression of key genes in dopaminergic neurons.
Crucially, the team was able to confirm that the neurons produced were of the same type as those found in the ventral midbrain, where the substantia nigra is located, highlighting the potential for this discovery to be used to treat Parkinson’s disease. In a statement, co-author Jian Feng insisted that that the new method is “faster and much more efficient than previously developed ones,” explaining that the team was able to convert 60 percent of skin cells into neurons over a period of 10 days. Prior attempts to do so had been considerably lengthier and less productive, generally achieving a conversion rate of just 5 percent over two weeks.
While more work is needed in order to devise new treatments from this research, the study's authors conclude that it could well be used to create patient-specific neurons not only for personalized therapy, but also for research into Parkinson's.
