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In Parkinson's disease, certain kinds of neurons die over time, but it might be possible to reprogram other types of cells in the brain to replace those lost ones.

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This episode is brought to you by Sanvello.

To get started with the Braving Anxiety journey, you can download the Sanvello app or  click the link in the description. [♩INTRO]. In 2020, researchers did something that  sounds straight out of a sci-fi movie.

In experiments on mice, they took  a type of cell called a glia cell, and they transformed it into a neuron. In a sense, they took one kind of body  part and turned it into another one. And apart from being amazing,  this technology could potentially reverse symptoms of Parkinson’s Disease.

Parkinson’s is characterized by the death  of a population of neurons that produce dopamine — a neurotransmitter that  regulates movement, among other things. That’s why the disease causes  symptoms such as tremors and difficulty with motion. Today, we have medications  that keep Parkinson’s at bay.

But they eventually stop working as  the dopamine-producing cells die off, since drugs can’t work if  there’s no target cell to act on. One solution scientists have talked  about here is stem cell therapy. Stem cells are sort of a blank  canvas.

They’re undifferentiated, which means they can turn  into a variety of cell types. So, if stem cells were used in a treatment, some of them could transform into  neurons to replace the dead ones. But accessing stem cells is difficult.

It can require a bone marrow transplant  or harvesting cells from fetal tissue, both of which come with their own challenges. So, a much more appealing  approach would be to reprogram a patient’s existing cells to start  making dopamine again… somehow. It’s a tall order, but scientists have  actually figured out how to do that using, of all things, viruses and bacteria.

One technique they’ve used  utilizes AAV technology. The AAV stands for adeno-associated virus. These viruses don’t cause human  diseases, so they make great lab tools.

Like any virus, they insert  their genes into a host cell, and the host cell follows  those genetic instructions. Normally, the instructions tell the  cell to start assembling more copies of the virus, so the virus can replicate  and continue infecting something. But in this case, researchers can  edit the genes carried by the AAV, and provide new instructions to tell  the cell what to make or how to behave.

The second technique is a newer  gene-editing technology called CRISPR-Cas9. With CRISPR, scientists program a bacterial enzyme to act like a pair of very precise  scissors that snip out specific genes. The trouble is, there isn’t just  one gene behind Parkinson’s Disease.

And we don’t understand the  disease well enough to go in and somehow rescue those dying  dopamine cells with AAVs. But we may be able to use these  techniques to replace the neurons. And that brings us back to 2020.

In papers published that year, two  research groups did just that by using AAV or CRISPR to make a simple  genetic edit in glia cells. Glia are support cells for neurons. Among other things, they provide  electrical insulation, clear up excess neurotransmitters, respond to brain  injuries, and form the blood-brain barrier.

In fact, there are probably  almost as many glia in your brain and nervous system as there are neurons! And in their study, scientists were  able to convert glia into neurons by decreasing, or knocking down, the  activity of just one small gene family, called Ptbp. Depending on the study, they  did this by either using AAV to inhibit their target gene, or  CRISPR to cut it out completely.

Now, the fascinating thing is,. Ptbp isn’t actually related  to Parkinson’s or dopamine. Instead, this group seems to be  involved at an early developmental stage in determining which cells  become neurons and which don’t.

And when one of these genes  is blocked or edited out, that stops a cell from producing a  specific protein — and changes its destiny. In these studies, scientists  transformed glia cells into neurons that had all the typical features you’d expect:. They produced neuron-like electrical signals, expressed neuron-specific  genes, and even made dopamine.

That part is especially cool, because  not all neurons produce dopamine. But in this case, the former-glia cells  got the memo to fill that specific role maybe from signals in the  neighboring brain region. The coolest thing of all, though, is that  this didn’t just happen in a petri dish.

The scientists used this technique on  live mice with Parkinson’s-like symptoms. And over time, the treatment  returned the mice’s dopamine levels and movement ability to normal. Which is incredible.

Now, if glia are so important,  it might seem unwise to transform some of them into neurons. But luckily, new glia are reliably  produced throughout adulthood, so swapping a few of them  shouldn’t pose a long-term problem. And in other cases, scientists can also change other kinds of cells into neurons,  too — including cancer cells.

Other researchers have converted a  carcinoma cell line into neurons, using a similar editing technique  to tweak this same gene. So this kind of technology may have  applications even far beyond Parkinson’s. That said, clinical applications will  still have to be developed and tested.

Before this could become a  viable therapy in humans. We are talking about some pretty  serious brain surgery here. Drilling a hole into someone’s  skull is no simple feat.

And injecting gene-editing vectors  into the brain is a delicate procedure! Still, this is a big step in our  understanding of how brain cells develop. And it’s a huge leap towards curing  Parkinson’s and similar diseases.

The human brain is complex, but it’s  also something we can understand. And that’s true for the feelings we  experience as well, including anxiety. Feeling anxiety is completely normal, but can be a lot more useful in  some situations than in others.

And if you want to learn more about that, you can check out the “Braving  Anxiety” journey on the Sanvello app. It’s hosted by none other than John Green, who takes you through an  expert-designed program to help you recognize triggers and thinking traps,  plus help you reduce stress and anxiety. The app is ranked #1 for stress, anxiety,  and depression, and you can download it for free in your app store or by  clicking the link in the description. [♩OUTRO].