Parkinson’s Disease: Can Stem Cells Help?

Parkinson’s Disease is serious, y’all. And I don’t really like to write about serious things, because they’re real. They impact people’s lives. And break hearts. And test limits. And forge humans out of steel.

But today I’m going to discuss Parkinson’s Disease, because someone emailed me about it a week ago. And I don’t believe they’re alone in their line of questioning. And really this is why I made this blog. It can’t always be the top five reasons you shouldn’t listen to Gwyneth Paltrow about literally anything outside of hair care.

Here’s what you need to know: the malfunction that causes Parkinson’s, how we currently treat it, and whether or not it makes sense to use stem cells (or other cutting edge technologies) to improve upon current treatments.

So let’s jump right in.

Parkinson’s Disease Lives In A Small Cell Cluster

in the brain. Even now, as an all grown-up scientist minded person, I find it hard to believe that such a tiny structure can cause such big problems. But it does.

This awesome animation from Khan Academy does a great job of explaining the crux of the issue. At least the part of it that we understand. In a nutshell, this small cell cluster in the mid-brain, the substantia nigra, loses cells that make dopamine. The decrease in dopamine leads to the physical symptoms of Parkinson’s Disease, like tremors and slow/difficult movement.

So really, Parkinson’s Disease comes down to brain cells dying when we really need them to stay alive and keep making dopamine. But there is good news:

We Have Great Medications for Parkinson’s Disease

Even though Parkinson’s is a progressive, degenerative condition, we do have awesome medications for it. See, we know that loss of dopamine is the biggest issue. And physicians have actually been treating that symptom of PD for over forty years in a couple of different ways.

Dopamine Agonists

These are sort of the expendable crewmen of Parkinson’s treatment. Dopamine agonists have some of the same effects as dopamine and can control the early stages of Parkinson’s symptoms. And there are so many of them that I’m not going to bother listing any.

Long story short: dopamine agonists comprise the first line of Parkinson’s defense and can work well in the early stages after initial diagnosis.

L-Dopa

Y’all know your brain runs your whole body, right? So your body has several ways of protecting it, one of which is the blood-brain barrier. This intricate biological system guards the  brain, much like the kind of security you’d expect to see in important government buildings. Only things that really need to be in the brain get through.

So if we want to put dopamine in the brain to treat Parkinson’s, we have to find a way to get it past the blood-brain barrier. Because the brain thinks dopamine comes from the brain, so it doesn’t have a natural mechanism for allowing it past the barrier.

That’s where this awesome molecule (that I used SO much in grad school) comes in. Levodopa, or L-Dopa, easily crosses the blood-brain barrier and is converted to dopamine in the brain. Which then leads to a decrease in Parkinson’s symptoms.

But. Only a small percentage of L-Dopa crosses into the brain, leaving the rest of it bumping around in parts of the body where it isn’t needed. And can cause unwanted side effects when it converts to dopamine.

So for Parkinson’s, L-Dopa usually comes with a couple of other drugs that (1) don’t cross the blood-brain barrier, and (2) prevent the conversion of L-Dopa to dopamine. This way you get more dopamine in the brain, where it’s needed, without getting more dopamine in the rest of the body where it’s not.

Now, as with many things in your body, continued use of L-Dopa combined with progressive loss of dopamine producing cells can lead to “tolerance” of lower doses. So most patients will end up increasing their dosage over time, eventually leading to a point at which they are experiencing unwanted side effects due to the high dosage.

This is usually the point at which patients begin looking at more aggressive treatment options, including the addition of some of the prescriptions below.

Others

MAO-B Inhibitors: MAO-B stands for a really long enzyme that breaks down dopamine. When we inhibit that enzyme in the brain (with MAO-B Inhibitors), dopamine should stick around more. And symptoms of Parkinson’s should decrease. These guys do present more of an issue though, because they cause more side effects than dopamine agonists.

COMT Inhibitors: You probably guessed it, but COMT is short for an enzyme that breaks down dopamine. So same story here as directly above. The idea is to inhibit the thing breaking down dopamine, thereby increasing dopamine. These are used less frequently than other options due to side effects and lack of efficacy.

Physicians may also treat psychosis, dementia, and excessive sleepiness with a cocktail of other drugs. But those are really aimed at some of the downstream effects of Parkinson’s and not the cause (lack of dopamine).

So what happens when a person has been treated with these great drugs for so long that they’re no longer effective?

Physicians and patients start looking into surgical answers. And the surgical answers are pretty remarkable.

We Have Awesome Surgery for Parkinson’s Disease

Remember earlier how I said that PD comes from a tiny cell cluster in the brain? I’m going to see if this link will show you that cell cluster.

Side note: my single favorite way to understand anatomy is Zygote Body. It really helps visualize some of the things, especially brain structures, that are hard to understand without three dimensional information. 

Ok, that link won’t show you what I want. But, if you click the link and then type “substantia nigra” into the search bar on the top right, it’ll label the right structure for you.

Ok, now that you’ve seen the size of this cell cluster, let’s move into how the surgical option works. No, surgeons don’t implant a time release dopamine device. Or nanobots that make dopamine.

It turns out that electrical impulses can actually make up for the loss of dopamine. Crazy, right?

But not really. Because almost every cell in your body depends on very tiny electrical impulses. So even though dopamine is the problem, electrical stimulation can be the solution. Because when functioning correctly, the dopamine should control electrical impulses in charge of physical movement (in that part of the brain).

If electrical impulses work, then how do we get them into the Parkinson’s causing part of the brain?

surgeons Place Tiny Implants In The Brain

You read that right. I know it sounds scary, but surgeons have gotten really good at this. Plus the implant itself is like a piece of cooked spaghetti. Here’s how it works:

  1. Doctors take a ton of pictures of your brain and map out every blood vessel, structure, and fold.
  2. Doctors use all of those pictures to make a 3D model of your brain.
  3. Using the 3D model, a pathway is marked out from your skin all the way to the target cells. This pathway avoids all important structures and essentially makes a beeline direct from your skin to the target location.
  4. At the beginning of surgery, you put on a special crown. This crown orients your brain in surgery to the pictures of your brain in the 3D model. That way the surgeon is certain that the planned starting and ending points are exactly the same in surgery as in the plan.
  5. Once surgery begins, your surgeon uses a robot to slowly guide the tiny spaghetti like implant down the planned path.
  6. As the final location approaches, your surgeon will test the implant. So yes, you’ll be awake. This testing phase ensures that the implant is in the most beneficial location for your specific brain anatomy.
  7. Once the surgeon finds the optimal location, they attach the spaghetti to a tiny anchor just outside your brain. This keeps the implant still and ensures your movements don’t ever affect the implant location.
  8. The last part of surgery is attaching the end of the piece of spaghetti to a small battery, and then implanting that battery. Most people put the battery in their chest or abdomen, and they’re so small now that you really have to know where they are to find them. Much like pacemaker batteries.

Here’s a creepily silent animation that shows an example of where this type of implant goes.

Now, because this implant requires brain surgery, the surgeon doesn’t turn it on immediately. So even though it’s physically in the right place, most surgeons will wait a couple of weeks before turning it on. This ensures that your body has had time to calm down after surgery.

Once those couple of weeks pass after surgery, a neurologist will program the implant. This process just tells the implant how much electricity to use in which part of the implant to give each patient the best result.

So what is that best result?

Brain Implants Are Crazy Effective

This video demonstrates how incredible these implants are. And he comes right out and says it.

It’s life changing.

But wait – where’s the science? Ok, let’s check the literature to see how effective these implants really are.

In this review, published this year, the authors looked at twelve different studies including 401 patients. They wanted to see if the effects of L-Dopa and brain implants were better together or possibly separately. They found, as you might expect, that both treatments decreased the physical symptoms of PD. But, when used together, patients experienced a 35 point improvement on a Parkinson’s Disease rating scale versus only about a 20 point improvement when either treatment was used separately.

That’s on the order of 50% more effective when combined than when  used separately.

Note: this review article included data up to five years out from surgery. And, some of the implants used would have been less advanced than the ones we have now. So I personally would expect some patients to have even better outcomes than what this review included.

Stem Cells for Parkinson’s Disease?

I know I’ve just sold you on the epic nature of brain implants for Parkinson’s. And you’re probably thinking we don’t need stem cells anymore. Especially if you watched this video all the way through. But, let’s revisit one important point.

Every treatment I’ve listed thus far treats a symptom of Parkinson’s Disease, not the underlying cause. Which means that every treatment, even life-altering brain implants, doesn’t really present a solution.

That’s where people tend to lean toward stem cells. Because they can become other kinds of cells, right? Like maybe dopamine producing cells?

Maybe. At this time, I’m not aware of anyone actually creating dopamine producing cells from any adult stem cell. But that doesn’t mean it’s not happening. It might be. [edit: it is happening. Here. And here.]

Let’s focus on a more realistic role for adult stem cells though. Remember when I listed the functions that make mesenchymal stem cells (MSCs) so useful? Let’s speculate wildly* for a moment about how those properties might help with Parkinson’s Disease.

*Note: wild speculation is not science. It is the combination of imagination with substantial education. So wild speculation may turn out to be true, and it may not. You’ve been warned. 

Now back to that speculation.

Ways MSCs Might Help with Parkinson’s
  1. MSCs save dying cells. Dopamine producing cells die in PD, causing physical symptoms.
    Maybe MSCs could save some of those cells, slowing down or stopping the progression of PD at the root.
  2. MSCs control inflammation. Inflammation occurs in the same area in which dopamine producing cells die. Some researchers have even declared that inflammatory processes are “crucial for disease progression.”
    Maybe MSCs could control or eliminate the inflammation, thus depriving the tissue of one crucial component for PD progression.

But what about other stem cells? Could they help too?

Maybe.

And you’ll find the mechanism of their help pretty obvious. Other stem cells, possibly manipulated MSCs or iPS cells (which I’ll still talk about in a later post) could maybe be programmed to produce dopamine. Basically these manipulated stem cells would attempt to replace the damaged or dead cells in the brain. And as such could represent a more long-lasting treatment option than some of the pharmaceuticals currently in use.

But that goes for all of the cell-based treatments. Any time we can get a living cell to go stay in a damaged tissue and do the job that tissue needs, that solution lasts longer than any non-cell based solution. Because cells maintain themselves much longer than any implant or drug can.

Alright. Now that we’ve speculated wildly, let’s take a look at what people have actually done with stem cells and Parkinson’s Disease.

Stem Cells Have Been Used to Treat Parkinson’s Disease

In 2010, this group published a study with follow-up at the three year point for some of their patients. Now, you must pay attention to how they implanted the cells here, because they did it right. This group used the same brain surgery approach I described earlier for those spaghetti noodle implants, but instead of those implants, these guys placed MSCs from the patient’s bone marrow in the target area.

very important note:

Every time someone uses stem cells, or a drug, or anything to treat anything in the human body. In order for it to work, they must first figure out how to get it where it needs to go.

So when someone says they want to treat Parkinson’s Disease, they need to figure out how to get their treatment into the specific area of the brain where we know the cells are dying.

And that’s a challenge. Because the blood-brain barrier is legit. It lets very few things pass. Imagine it as Gandalf just constantly yelling YOU SHALL NOT PASS at almost everything. Including stem cells. Stem cells CANNOT pass the blood-brain barrier. They’re too big.

So when you read about someone using stem cells to treat Parkinson’s Disease, you should be looking for an actual brain surgery to get those cells where they need to be.

end very important note

As I was saying, this group did it right. They used brain surgery, just like the one used for PD electrical spaghetti noodle implants, to get the cells where they needed. Three of the seven patients treated showed steady improvement in the Parkinson’s Disease Rating Scale assessments, improving on average 22.9% from before treatment. Two of those patients also significantly reduced their medications.

Members of that same group did another study in which 12 patients ranging from 5 – 15 years after PD diagnosis were treated with MSCs not from their own bone marrow. Again, this group implanted the cells using an appropriate brain surgery technique. One subset of patients, basically with standard PD diagnosis, improved 17.92% during “on” (meaning effectively medicated) state and 31.21% during “off” state. But some of the patients in this study didn’t improve at all.

And that’s one of the things about early research. We don’t always know why certain patients didn’t respond. Eventually an explanation will surface. But we have to do more studies to figure that out. And eventually we’ll get more patients with improvement and less patients who just don’t respond. Or at least we’ll be able to better predict when patients aren’t good candidates.

Let’s talk about one last study real quick. This one used highly manipulated stem cells programmed to become neural stem cells. The researchers used the same brain implantation technique we’ve discussed to place the neural stem cells in the brains of African green monkeys with Parkinson’s Disease. Twelve months after implantation, the monkeys had behavioral improvements, increased dopamine levels, and increased numbers of dopamine producing neurons.

I know this research sounds cool, and I’m hopeful that we’ll see some of the MSC based therapies in the regular world within the next ten years. The results thus far are definitely promising.

But. Right now this stuff falls into the research category. It’s not ready for prime time yet.

It will be. In our lifetimes. Just not right now.

People Should Not Be Selling Stem Cells for Parkinson’s Disease

Did you notice the common thread among the studies I covered? Every single one of them used brain surgery to place the cells. Right now, that’s the only surefire way to get stem cells to the tissue affected by Parkinson’s Disease.

So if you happen to search for a PD treatment and find someone offering stem cells for it, I hope you’ll first check to see if they’re a neurosurgeon. Specifically one specializing in stereotactic brain surgery (the technical term for the type of surgery we’ve discussed multiple times in this post).

If a chiropractor, pain management doctor, orthopedic surgeon, witch doctor, naturopath, shaman, priest, or alien offers you a stem cell treatment for PD, please don’t mortgage your house for it. Please don’t use your kid’s college tuition for it.

Please ask a thousand questions, the most important of which are: how will this get to my PD cells? How many times have you done this before, and what were the results? Is this part of a clinical study? How do you know this is safe?

If someone offers you or a loved one a stem cell treatment for PD outside of a clinical trial or study, without the help of a neurosurgeon, you should not expect success. Or safety.

In case there’s any lingering doubt, my personal favorite PD treatment is the electrical spaghetti noodle implant. They do amazing things and have a long history of safe and effective use.

I’m excited to see stem cells come onto the PD field in the near future. I really am. But I know they aren’t ready for general clinical use in Parkinson’s Disease just yet.

Have you heard of any other cutting edge PD treatments? Or something crazier than stem cells that you think is a pack of lies? Let me know in the comments, or send that info direct to my inbox!

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