Approach that inspires DREADD could create new way to treat Parkinson’s disease

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Dopamine producing brain nerve cells, made from embryonic stem cells

Imagine having a treatment for Parkinson’s that acts like a light switch, enabling you to turn it on or off depending on your needs. Well, that’s what researchers at the University of Wisconsin-Madison have come up with. And if it works, it might help change the way we treat many other diseases.

For years researchers have been trying to come up with a way of replacing the dopamine-producing brain nerve cells, or neurons, that are attacked and destroyed by Parkinson’s. Those cells regulate movement and as they are destroyed they diminish a person’s ability to control their body, their movement and even their emotions.

Attempts to transplant dopamine-producing cells into the brains of people with Parkinson’s disease have met with mixed results. In some cases the transplanted cells have worked. In many cases the cells don’t make enough dopamine to control movement. In about 10 percent of cases the cells make too much dopamine, causing uncontrolled movements called graft-induced dyskinesia.

But now the researchers at UW Madison have found a new approach that might change that. Using the gene-editing tool CRISPR (you can read about that here) they reprogrammed embryonic stem cells to become two different types of neurons containing a kind of genetic switch called a DREADD, which stands for designer receptor exclusively activated by designer drug. When they gave mice the designer drug they created to activate DREADD, one group of cells boosted production of dopamine, the other group shut down its dopamine production.

In a news release about the study, which is published in the journal Cell Stem Cell, lead author Su-Chun Zhang says this kind of control is essential in developing safe, effective therapies:

“If we are going to use cell therapy, we need to know what the transplanted cell will do. If its activity is not right, we may want to activate it, or we may need to slow or stop it.”

Zhang says the cells developed using this approach have another big advantage:

“We can turn them on or off, up or down, using a designer drug that can only act on cells that express the designer receptor. The drug does not affect any host cell because they don’t have that specialized receptor. It’s a very clean system.”

Tests in mice showed that the cells, and the designer drug, worked as the researchers hoped they would with some cells producing more dopamine, and others halting production.

It’s an encouraging start but a lot more work needs to be done to make sure the the genetically engineered stem cells, and the designer drug, are safe and that they can get the cells to go to the part of the brain that needs increased dopamine production.

As Zhang says, having a method of remotely controlling the action of transplanted cells, one that is reversible, could create a whole new way of treating diseases.

“This is the first proof of principle, using Parkinson’s disease as the model, but it may apply to many other diseases, and not just neurological diseases.”

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