Episode 5: Is the nSTRIDE Injection the Future of Knee Osteoarthritis Treatment?

In this episode, Dr Karmy will take an in-depth look at the newest treatment for osteoarthritis—the nSTRIDE Autologous Protein Solution (APS) kit. Like Platelet Rich Plasma (PRP), this treatment is made from the patient's own blood. 

How does it compare to PRP?  Is it worth trying? Dr. Karmy will not only explain the science behind nSTRIDE from existing clinical literature but also share insights from his own research and patient experiences.

Follow our social media:
Instagram
https://www.instagram.com/karmychronicpain?igsh=cHZycXdzeGhqN2Zn
Facebook
https://www.facebook.com/profile.php?id=61550237320641&mibextid=dGKdO6

Learn more about pain management treatments offered at our clinic: https://karmyclinic.com/

Chapters

• 1:11 PRP: Protocol, Applications, Mechanism of Action, White Blood Cell and Platelet Concentration Controversies
• 8:16 nSTRIDE: Comparison with PRP Treatment, Cell Composition Analysis, Protocol, Variability in Clinical Response Rates, Limitations of Research Studies
• 19:42 Combination Therapy of PRP and nSTRIDE: Dr Karmy’s Hypotheses
• 22:24 Future of nSTRIDE, Insurance and Provincial Coverage

Transcript

nSTRIDE has primarily anti inflammatory cytokines, which reduce inflammation and reduce damage to the cartilage, slow down progression of osteoarthritis. 

Welcome to Chronic Pain Chronicles with Dr. Karmy, where we embark on a journey to uncover the transformative potential of regenerative medicine in chronic pain management. I'm Raveena, your host and guide through the intricacies of this evolving field. Today, Dr. Karmy explores a novel, cutting edge innovation that's making waves in treating knee osteoarthritic pain, the nSTRIDE Autologous Protein Solution, aka the nSTRIDE APS Kit.

This novel regenerative approach harnesses the body's healing capabilities to offer relief and improve the quality of life for chronic pain patients.  As we navigate the landscape of pain management, we're privileged to be joined by Dr. Karmy, a seasoned expert in pain management with over two decades of medical experience. 

Hello, this is Dr. Karmy, and today I wanted to discuss an interesting topic that I touched on briefly in my previous episode. We have PRP,  which is a blood based treatment for osteoarthritis.  And we have nSTRIDE, which is a more recent  treatment, which is also created out of patient's own blood.  Just how much difference is there between these two approaches?

Well, let me start with platelet rich plasma. This is the older approach for 30 years.  What we do with platelet rich plasma is we extract blood from the patient. How much blood we extract varies a great deal depending on the protocol people use. It can be as little as 10 milliliters and as much as 50 or 60 or 80 milliliters.

So it's more than you would, you would get taken in a case of doing  blood work, but it's a lot less than the amount of blood you would donate if you went for a blood donation.  Then you spin the blood in the centrifuge and your goal is to separate platelets which are components of the blood, which stimulate clot formation from all the  other components. Sometimes you can do that by spinning the blood once, and sometimes you have to spin the blood twice. Then you separate the layers that contain platelets from layers that contain predominantly red cells, which are important for transporting oxygen throughout the body.  And you inject that mixture, which typically you have is about 10 mils to 5 mils or 4 mils.

You inject that into damaged joints or tendons or ligaments or muscles or even around nerves.  Platelet rich plasma (PRP) has been used for a very wide variety of conditions, ranging from the areas of pain I mentioned, to hair regrowth, to cosmetics, to  erectile dysfunction or even injections into vaginal lining.

This is, as I mentioned, a relatively older treatment, and there has been a lot of debate as to whether it works, how it works, why it works.  Typically, the product that you get with PRP has a lot of platelets.  In addition to that, often, the product that you get contains a lot of white cells. So, most people feel that platelets are beneficial. 

They release some growth factors which stimulate patients own stem cells to divide. They also release some anti inflammatory factors.  But there has been a lot of debate about white cells. White cells are immune cells, normally they protect your body against infections, and frequently, but not always, they are found in platelet rich plasma preparation.

There's one group of physician researchers who feel that white cells in platelet rich plasma are bad because they cause additional inflammation and potentially tissue damage. There's another group of physicians that feel that white cells actually make PRP stronger because the same white cells can release anti inflammatory growth factors.

So there's been a lot of debate back and forth.  One issue is that perhaps the target makes a difference. There is some discussion about the fact that maybe, if you're injecting tendon, white cells are okay, but if you're injecting  a joint with cartilage, perhaps you don't want any white cells. The other issue  is that when you centrifuge blood, often white cells end up very close to the layer where most of the platelets are. 

And if you are trying to produce platelet rich plasma without white cells, invariably you lose a lot of platelets. In other words,  platelet rich plasma, which is glucoside poor, or sometimes we call it pure PRP, which doesn't contain white cells, invariably contains fewer platelets too. And if you believe that the more platelets you have, the  better your results are going to be.

It makes it difficult to have it both ways. In other words, have a lot of platelets and have no white cells. How many platelets do you need in order to have a good response to PRP?  Again, this is up for debate, but the latest set of ideas is that you need  5 billion platelets per knee. or more and perhaps the numbers for other big joints like shoulders and hips are similar.

Now let's look at nSTRIDE. And I have injected patients with ENTs tried in the past. It's a relatively newer treatment. It only came out in 2020, around the same time as pandemic hit. It is produced by a major medical device company, Zimmer Biomet. Zimmer Biomet is a huge publicly traded company worth billions of dollars. 

Traditionally, it makes equipment for orthopedic surgeons that they use for treatments like knee replacements. However, more recently, it has decided to  also get into regenerative medicine field and nSTRIDE is one of its first partners. products. They also have a platelet rich plasma product, and they also have a bone marrow concentrate product.

However, today we will focus on nSTRIDE. So, first of all, how different is nSTRIDE from PRP? Well, we have reviewed the literature provided by the company,  but more importantly, we also analyzed nSTRIDE ourselves. We only started this process, so only have a few patients that I have analyzed,  but on the basis of what I see so far, nSTRIDE is unapologetically in the camp of physicians who believe that white cells are good  and essential for treatment of osteoarthritis. When you look at cell composition in platelet rich plasma, and we have looked at cell composition  of platelet rich plasma produced by multiple manufacturers, what you typically see is, of course, high platelet count.

You also see an elevation in lymphocyte number, which is one type of white cell or immune cell. And often you see elevation in monocyte number, which is a different type of immune cell. And then there's a third group of cells called granulocytes. And typically those ones get washed out and the levels of those are low in platelet rich plasma. 

When you look at cell composition of nSTRIDE, the picture looks very different.  First of all, although platelets are elevated, compared to baseline, in most cases they are just slightly elevated. So as a PRP, it's a pretty weak PRP.  What you do see, however, is striking elevation in white cells. And not just the lymphocytes and monocytes, but in the two out of the three cases we analyzed, granulocytes are very significantly elevated.

So, on the basis of cell composition, they look very, very different. This is almost a pure play on benefits of white cells. With, you know, perhaps a little bit of contribution from platelets. It's also produced differently. You start by actually by producing platelet rich plasma,  but then you use beads to stimulate the white cells to release some of the anti inflammatory factors or cytokines,  and then you spin it the second time around and isolate those white cells with a few platelets. So the total volume of the fluid you inject is a lot less than with platelet rich plasma. Typically, it's around 2 to 3 milliliters compared to 6 to 10 milliliters of PRP.  According to the manufacturer, also the composition of  cytokines or chemicals in that fluid is quite different.

It  has a lot of cytokines which are anti inflammatory or reduce inflammation, which hopefully reduces further damage to the joint cartilage. There's a lot of ideas that the reason that patients develop joint cartilage and wear and tear is because of inflammatory environment in the joint. So what about the responses  to nSTRIDE?

Well, I have been to a recent conference where  nSTRIDE was discussed  and according to them the response rates are 70 percent of patients have their pain reduced by 70 percent at the one year mark and 60 percent of patients find that their pain is reduced by 60 percent at a five year mark. So it seems at least based on those figures And these are provided by the manufacturer that there's a fairly high response rate at a one year point, and it starts to wane slightly, but nevertheless, the response remains fairly strong for as long as five years.

I don't think they have had a chance to really look much longer than that. How reliable are those numbers? Well, you know, I think they should be taken with a grain of salt. First of all, these numbers are based on multiple studies looking at different things. The number of patients in total is fairly large, 820 patients.

However, split between different studies and different protocols often makes it harder to draw conclusions.  Also, with any pain treatments, often the placebo effect is at least as large, if not larger, than  the actual benefit of any given treatment. Placebo effects are huge in pain trials and typically very hard to avoid.

Finally, all these studies are funded by the Zimmer Biomet who manufacture nSTRIDE.  And although I can't make any comments about these particular studies, there have been more broader studies looking at comparing studies funded by a pharmaceutical company to studies funded by some neutral government agency like NIH  and what they found not terribly surprising is that typically studies that are funded by the drug manufacturer have a lot more positive outcomes than studies funded by a neutral party.

One other interesting topic that perhaps I should mention, and that is that nSTRIDE doesn't help everyone. I think I mentioned this before, but there's an additional interesting wrinkle here. As I mentioned, nSTRIDE Depends on your immune cells releasing anti inflammatory factors. Well, white cells have multiple functions, and I think the best analogy would be an army. 

An army in some situations, say in war, might destroy cities and kill people, whereas in other situations such as hurricane or some other natural disaster, the army might be brought in to save people, to provide supplies, to provide shelter. So depending on the situation, army can have very different functions.

Well, your immune system is sort of like an army. And when it's exposed to bacteria or viruses, it releases a lot of pro inflammatory factors, which lead to a lot of damage and destruction. However, when whites, when there's a damage, the white cells will often go to the area and actually help reduce inflammation and stimulate healing.

So the environment determines how the white cells behave. They can either be pro inflammatory or anti inflammatory. And at the conference, what was noted is that patients who have already. Pro inflammatory  condition in the blood, or I should say in the body, such as rheumatoid arthritis, for example,  or some other inflammation going on. 

If you inject nSTRIDE in those people, instead of getting better, They actually get worse. So I guess another  fine point in terms of response rate, if patients have any kind of inflammatory disorder such as lupus or rheumatoid arthritis or Crohn's disease.  Or even if in their blood  they have elevated inflammatory markers such as ESR or C reactive protein, perhaps nSTRIDE is more likely to do harm than good.

So what about combining platelet rich plasma and nSTRIDE? So, first of all, there have been no studies looking at that question. So this is purely speculative, based on logic, and logic unfortunately fails often in biology. Having said all of that, there is some reason to think that combination may be useful.

As mentioned earlier, well, nSTRIDE and platelet rich plasma seem to be distinct treatments with distinct chemicals or cytokines. nSTRIDE has primarily anti inflammatory properties cytokines which reduce inflammation and hopefully reduce damage to the cartilage and slow down progression of osteoarthritis.

Platelet rich plasma has some anti inflammatory chemicals or cytokines.  But not as many, but what it does have is a lot of growth factors which stimulate division of stem cells. So treatments seem to be complementary and it is possible that combining them would provide better or stronger result than each one separate. This is especially true in large joints like hips, for example generally speaking for most regenerative medicine treatments response to hip injections is very, very worse, or lower response rate than injections for knees, so it's often a difficult joint to get a good response with, and equally importantly, the joint space is very large, and as I mentioned, joint nSTRIDE only has 3 milliliters of fluid in it.

So it may be difficult for N stride to spread out throughout the joint, whereas platelet rich plasma, you typically have much larger volumes of product, maybe 6, maybe even 8 mils, perhaps something there, especially in more difficult to treat joints. What about future specifically for N stride?

Well, there's several aspects of nSTRIDE that I find interesting. One of them is that unlike PRP,  which is used very widely for everything ranging from joint pain to tendon pain to nerve pain, hairy growth to cosmetics to erectile dysfunction and stride has really only been looked at  for knee osteoarthritis. 

So, one of the directions I suspect Zimmer Biomet will take this product is looking at other targets. In particular tendons and nerves often don't require a large volume of product, so it may be quite interesting to look at those potential targets. There's also  another aspect which I find really interesting and promising, and that is that nSTRIDE is the only one out of all the regenerative medicine approaches that has actually been approved by Health Canada for a medical indication.

It has an official approval for knee osteoarthritis. We use all kinds of other regenerative medicine treatments for all kinds of applications but they do not have that approval. So why is this important? This is important because if you want to get coverage or any kind of treatment, be it from an insurance company or in provincial insurance plan, you need to have that approval as a starting point. 

Now, this approval on its own is not sufficient. Often, it's a very long. A difficult process to get a treatment covered by an insurance plan, be it a private drug plan. or a provincial  plan or both. However, in this case, you have a multi billion dollar company behind this product who have the resources to make this happen.

The problem with most other regenerative medicine treatments, and I alluded to that in the past, is that nobody really owns it. Nobody has a patent on it, and therefore no one will invest the time, the money, and the effort to make it happen. To do the big studies required for these sorts of approvals, to spend the money lobbying and jumping through all the hoops to get all the necessary approvals.

Often it can cost millions of dollars and small clinics that provide regenerative medicine don't have that kind of money. And more importantly, often you have to spend money up front and you only see the returns over a number of years. And if you have a monopoly on a product, like a patent, as they do with nSTRIDE, then you are able to recoup your investment.

Whereas if you get an approval for something like platelet rich plasma product, for example, well, every single clinic that offers PRP will be competing with you. So it would be very hard to make your money back. nSTRIDE would face some unique challenges compared to nSTRIDE. Other products because nSTRIDE is something we make out of patient's own blood. It's not really a drug. It doesn't have a DIN number. So it would be a little bit of uncharted  territory. But having said all of that, I anticipate that there's going to be more and more of cell based.  products on the market in the future. And therefore, this is going to be a new category of products covered by insurance company.

For instance, I know that there are some immune cells called CAR T-cells that are modified to fight cancer that are being produced. There's also some treatments for blood disorder called sickle cell anemia, which involves injecting, I could be wrong, but I think it's a virus. into the bloodstream of a patient with sickle cell anemia, which will go to the cells which produce red cells.

The problem with sickle cell anemia is that red cells deform, they have an abnormal shape and that causes all sorts of problems. So, anyway, the virus goes towards cells and it changes them to produce a better version of red cells that don't have those problems. So,  although I have no indication that Zimmer Biomet is going there, at least they have the ability and the resources to try to get it covered either through drug plans or provincial insurance plans, or both. Thank you. 

Thank you for listening to the fifth episode of Chronic Pain Chronicles with Dr. Karmy, a podcast which explores chronic pain from a physician's point of view. Our episodes explore some of the most effective and commonly used approaches to managing chronic pain, including nerve blocks, platelet rich plasma injections and alternative medicine approaches. 

We will also explore the causes of chronic pain and understand where the field is going in the future, while also sharing real life stories that come directly from our patients. I am Raveena Aujla. Till next time.  Be sure to follow us on our social media platforms for the latest updates on pain management treatment and lifestyle pieces.

Our Instagram is at karmychronicpain and our Facebook is Karmy Chronic Pain Medical Clinic. We really appreciate it if you like and leave a review on our page.  

Disclaimer: When it comes to your health, always consult with your own physician or healthcare provider for personalized advice and guidance. The information provided in this podcast is for educational and informational purposes only and should not be considered medical advice or a substitute for professional medical care.