Researchers looking to treat Parkinson’s disease have been trying for years to develop a way to fix defective dopamine neurons, with efforts using fetal material and embryonic stem cells generating limited results.
The methodology is based on discovery that a transcription factor protein called p53 acts as a gatekeeper for the cell, keeping it from evolving into a different kind of cell. The study team found that lowering the expression of p53 allowed them to go in and reprogram the skin cells into something completely different.
Study author Jian Feng recently told redOrbit that his research team decided to use skin cells because of their accessibility.
“All we need is basically a small square, and you can get that very safely with a skin biopsy” said Feng, a professor of physiology at UB. “So this is a source of cells that can be harvested without too much pain, and very easily.”
Feng’s team had been working with stem cells, trying to convert them into functioning dopamine neurons. However, that process—which attempts to mimic early human development—is long and complicated.
“So we thought if we can do a direct conversion (without a stem cell stage), it would be a lot easier,” he said.
At first, the team only had about a five percent success rate at converting skin cells into neurons. Then, a paper came out in 2011 showing transcription factors capable of converting a human fibroblast into a dopamine neuron. Combined with the team’s earlier work that revealed p53 facilitated the transition of pluripotent stem cells, the new paper showed a feasible way to convert skin cells into dopamine neurons.
Timing is everything
The researchers found that the key to transitioning skin cells into dopamine neurons was getting the timing of p53 suppression just right. Feng noted that said skin cells are constantly sensing their environment for the signal to reproduce. For example, when you cut your skin, growth factors are released to tell the nearby skin to begin healing. It turned out that right before the skin cells “listen” for growth signals, they are open to change via the suppression of p53.
“I think that this is a generically applicable method that allows us to make all sorts of hard-to-get cells from an easy to get cell,” Feng said.
As for curing Parkinson’s, Feng said efforts must now focus on being able to grow A9 dopamine neurons, which a specifically implicated in the degenerative nervous system disorder. A9 neurons must produce massive amounts of proteins to function and self-sustain.
“This neuron lives in the body for let’s say 80 years, if someone lives 80 years, and during this time it has to constantly make proteins, lipids, and many other things,” Feng said. “So that’s mean the genome of this neurons is responsible for churning out all these protons. So if we can convert a cell into that kind of state, then we should be able to cure Parkinson’s disease, I think.”
Feature Image: University at Buffalo