Creating an on-off switch to test stem cell therapy for Parkinson’s Disease

Sometimes you read about a new study where the researchers did something that just leaves you gob smacked. That’s how I felt when I read a study in the journal Cell Stem Cell about a possible new approach to helping people with Parkinson’s Disease (PD).

More on the gob smacking later. But first the reason for the study.

We know that one of the causes of Parkinson’s disease is the death of dopamine-producing neurons, brain cells that help plan and control body movement. Over the years, researchers have tried different ways to try and replace those cells but getting the cells where they need to be and getting them to integrate into the brain has proved challenging.

A team at the University of Wisconsin-Madison think they may have found a way to fix that. In an article in Drug Target Review  lead researcher Dr. Su-Chun Zhang, explained their approach:

“Our brain is wired in such an accurate way by very specialized nerve cells in particular locations so we can engage in all our complex behaviors. This all depends on circuits that are wired by specific cell types. Neurological injuries usually affect specific brain regions or specific cell types, disrupting circuits. In order to treat those diseases, we have to restore these circuits.”

The researchers took human embryonic stem cells and transformed them into dopamine-producing neurons, then they transplanted those cells into mice specially bred to display PD symptoms. After several months the team were able to show that not only had the mice improved motor skills but that the transplanted neurons were able to connect to the motor-control regions of the brain and also establish connections with regulatory regions of the brain, which prevented over stimulation. In other words, the transplanted cells looked and behaved the way they would in a healthy human brain.

Now here comes the gob smack part. The team wanted to make sure the cells they transplanted were the reason for the improved motor control in the mice. So, they had inserted a genetic on-and-off switch into the stem cells. By using specially designed drugs the researchers were able to switch the cells on or off.

When the cells were switched off the mice’s motor improvements stopped. When they were switched back on, they were restored.

Brilliant right! Well, I thought it was.

Next step is to test this approach in larger animals and, if all continues to look promising, to move into human clinical trials.

CIRM is already funding one clinical trial in Parkinson’s disease. You can read about it here.

One thought on “Creating an on-off switch to test stem cell therapy for Parkinson’s Disease

  1. Although human and rat have high homologous of DNA genomes, but both have extremely different of promoter regulator to regulate gene expression. Molecule modelling research proved that regulation of immune system of rats and humans are inherently different. Evidence showed that the gene of Vitamin D Receptor (VDR) control the activity of human innate immune system and transcribes more than of 913 genes. It also controls the production of many antimicrobial peptides. These peptides kill bacteria, viruses and fungi by a variety of mechanisms. This is in contrast to the rat inate and immune system which is not controlled by VDR gene. Rats do have VDR gene, but they transcribe different genes from human. Therefore, the two species have different roles to kill invading pathogens, varying degrees in immunity development, activation and response to challenge in both inate and adoptive immunity. Thus, human immunity plays specific roles to reject all the foreign antigens from invasion but this is not seen in rat.

    Current research by using hESC to transplant into Parkinson disease (PD) models of rat can rescue motor defects of PD. Investigation also showed that similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural network, highlighting the capacity of hPSC derived neuron subtype for specific circuit repair and functional restoration in the adult brain.

    Humans and rats have extremely different immune system to eradicate the foreign antigens. Humans have strong and specific immunity to reject the invading of allogenic antigen but this is not seen in rats. Therefore, transplantation of hESC to cure PD rats does not translate the similar effective clinical treatment to cure PD in human. Many literatures reported therapies work well in mice but failed to provide similar efficiency in human. These observation highlights the risk of overlooking aspects of human immunology that does not occur or cannot be modeled in mice. Rhesus and Cynomolgus Macaqacas , African Green Monkey and mice are experimental models closely related to human but show numerous different cellular phenotypes and immune signaling events occurring within and between species.

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