PESTO Trial Results: What Stroke Survivors Need to Know About Perispinal Etanercept

If you’ve spent any time in stroke recovery communities, you’ve probably seen the same pattern: a treatment gets talked about with real intensity, people share personal stories that pull you in, and suddenly you’re left trying to sort hope from hype from “maybe.” When the decision also involves significant cost, that uncertainty can feel even heavier.

That’s exactly why I recorded this episode: to help stroke survivors and their families understand the PESTO trial results in plain language without drama, without attacks, and without jumping to conclusions.

In this interview, Professor Vincent Thijs explains what the PESTO trial set out to test, why it was designed the way it was, and what the results can (and can’t) tell us about perispinal etanercept in stroke recovery.

The real problem: not “hope vs skepticism”… it’s confusion

If you’re a stroke survivor, you’re already doing something heroic: you’re living inside a recovery journey that demands patience, grit, and constant adjustment.

The challenge isn’t that you “don’t want to believe” in something. The challenge is that it’s genuinely hard to make an informed decision when:

• People report different outcomes
  
• Online conversations become polarised fast
  
• Scientific studies use unfamiliar language
  
• The same treatment can be described in completely different ways depending on who you’re listening to
  

My goal here isn’t to tell you what to do. It’s to help you think clearly, ask better questions, and understand what the best available evidence from this trial actually tested.

What the PESTO trial was trying to investigate (in simple terms)

Professor Thijs explains that the PESTO trial was designed in response to strong community interest. Stroke survivors wanted to know whether the way perispinal etanercept is currently administered in some settings could be demonstrated to work under the standards used for medicines to become widely accepted as part of routine care.

So the researchers designed a randomized, placebo-controlled clinical trial. In this type of study:

• A computer assigns participants to either the treatment or a placebo
  
• Participants and clinicians are kept “blinded” (they don’t know who got what)
  
• Outcomes are measured in a consistent way at set time points
  

In the PESTO trial, the focus was on stroke survivors with moderate to severe disability and reduced quality of life. The primary question was straightforward:

Does quality of life improve after one or two injections compared with placebo, over the measured timeframe?

Why this study looked at quality of life (not one symptom)

One key detail Professor Thijs highlights is the design choice: the trial didn’t only target one issue, like pain or walking. It aimed to be more “pragmatic,” reflecting how treatment is used in real-world settings where people seek help for different post-stroke challenges (mobility, fatigue, speech, cognition, pain, and more).

That means the main outcome wasn’t “Did walking speed improve?” or “Did pain reduce?” It was broader:

• Quality of life at 28 days
  
• And again after the second injection timeframe (56 days total)
  

This matters because your results can look different depending on what you measure. A trial targeting one symptom might see a signal that a broad quality-of-life measure doesn’t detect (and vice versa).

What the PESTO trial results found

In Professor Thijs’ words, the trial did not show a difference in quality of life between the treatment and placebo groups at the measured time points:

• No clear quality-of-life improvement at 28 days
  
• No clear improvement after two injections at 56 days
  

That’s the central outcome.

But there’s another finding that grabbed my attention—and it’s one many listeners will find surprising.

Quote block (mid-article):

“We saw that 58% of the people also had that improvement [with placebo] and 53% had it with etanercept… our initial guess was very wrong.”

— Professor Vincent Thijs

The “placebo signal” and why it matters

A strong placebo response doesn’t mean “it was all in their heads.” It means that in a blinded clinical trial, people can improve for multiple reasons that aren’t specific to the drug itself, such as:

• Expectation and hope
  
• Natural fluctuations in symptoms
  
• The impact of being monitored and supported
  
• Regression to the mean (symptoms often move toward average over time)
  
• The structure and attention that come with trial participation
  

Professor Thijs describes how, during the blinded phase, participants reported improvements in a variety of areas (like sensation, vision, speech). The crucial point is: the team didn’t know who had a placebo or an active treatment at the time, which is exactly why blinding exists.

For you, the listener, this is a reminder of something empowering:

Personal stories can be real and meaningful—and still not answer the question of efficacy on their own.

“Am I a candidate?” The trial’s honest answer: we don’t know how to predict it (yet)

One of the most important parts of this conversation is the desire to identify who might benefit most.

Professor Thijs explains that the team looked at subgroups (for example: age, sex, severity, diabetes, time since stroke). In this trial, they didn’t find a clear subgroup where the treatment stood out as reliably beneficial compared with placebo.

He also adds an important caveat: subgroup analysis is difficult, especially in trials that aren’t extremely large. So the absence of a clear “responder profile” here doesn’t automatically prove none exists—it means this trial didn’t reveal one.

What this episode is (and isn’t) saying

Let’s keep this grounded and fair.

This interview is not about attacking any person, provider, or clinic. It’s not about shaming stroke survivors who tried something. It’s not even about telling you that you should or shouldn’t pursue a treatment.

It is about this:

• Understanding what the PESTO trial tested
  
• Understanding what the results showed within their timeframe
  
• Knowing the limits of what the trial can conclude
  
• Using evidence to reduce confusion before making big decisions
  

A simple “clarity plan” before you decide anything big

If you’re considering any high-stakes treatment decision, here’s a neutral, practical way to move forward:

1) Ask: “What outcome matters most for me?”

Is it pain? walking? fatigue? speech? cognition? daily function? quality of life?

A treatment might be studied for one outcome and discussed online for another.

2) Ask: “What does the best evidence say—specifically?”

Not “Does it work?” in general, but:

• In what population?
  
• Using what method?
  
• At what dose?
  
• Over what timeframe?
  
• Compared with what?
  

3) Ask: “What are my options and trade-offs?”

Talk with a qualified healthcare professional who understands your medical history, risk factors, and rehab plan. Ask about:

• Potential risks and side effects
  
• Opportunity cost (what else could you do with the same time, money, and energy?)
  
• Evidence-based rehab and supports that match your goals
  

Listen to the full interview

If you want the clearest explanation of the PESTO trial results—from the lead researcher himself—listen to the full episode with Professor Vincent Thijs.

And if you’d like to support the podcast (and help keep these conversations going for stroke survivors who need hope and clarity):

• Bill’s book: recoveryafterstroke.com/book
  
• Patreon: patreon.com/recoveryafterstroke
  

Medical disclaimer

This blog is for informational purposes only and does not constitute medical advice. Please consult your doctor before making any changes to your health or recovery plan.

PESTO Trial Results (Etanercept After Stroke) | Interview with Professor Vincent Thijs

Confused about perispinal etanercept after stroke? Prof Vincent Thijs explains the PESTO trial results clearly, calmly, and evidence-first.

More About Perispinal Etanercept:

Etanercept Stroke Recovery: Wesley Ray’s Relentless Comeback
Dwayne Semple’s Remarkable Stroke Journey and Perispinal Etanercept
Etanercept for Stroke Recovery – Andrew Stopps
Support The Recovery After Stroke Podcast on Patreon

Highlights:

00:00 Introduction and Overview of the PESTO Trial
04:19 Design and Objectives of the PESTO Trial
11:23 Recruitment and Methodology of the Trial
18:31  PESTO Trial Results and Findings
24:28 Implications and Future Directions for Research
32:15 Conclusions and Final Thoughts

Transcript:

Introduction: PESTO Trial Results

Bill Gasiamis (00:00)
Hello and welcome back to Recovery After Stroke. Before we get started, a quick thank you to my Patreon supporters. Your support helps cover the hosting costs after more than 10 years of me doing this show solo. And it helps me keep creating episodes for stroke survivors who need hope and practical guidance. And thank you as well to everyone who comments on YouTube, leaves reviews on Spotify and Apple podcasts.

buys the book and even to those of you who don’t skip the ads. Every bit of that supports keep this podcast going. Now today’s episode is about the PESTO trial results and I’m interviewing Professor Vincent Theis. If you’ve ever felt confused by the conversation online about perisponal antenna sept, some people sharing positive experiences while others are feeling disappointed and plenty of strong opinions in between, this episode is designed to bring

clarity. We talk about what the PESTO trial set out to test, how the study was designed, what it found within the measured timeframes and what the results can and can’t tell us. Just a quick note, this conversation is educational and not medical advice. Always speak with a qualified health professional about your situation. All right, let’s get into it. Professor Vincent Dase, welcome to the podcast.

Vincent Thijs (01:24)
Thank you for having me, Bill.

Bill Gasiamis (01:26)
I’m really looking forward to this conversation. Atenosept is one of the most hotly discussed topics in stroke recovery. And there’s a lot of misconceptions about whether or not it is or is not efficacious. And while there’s a lot of anecdotal evidence where some people have had positive outcomes from injections, there’s also a lot of people’s feedback, which is very negative about their experience with

the Etanercept injections and the lack of results. So today, the reason I reached out is because I wanted to get to the bottom of the findings of the PESTO trial. And I’m hoping that you can shed some light on that. The first question basically is, can you start by explaining in simple terms what it was that the PESTO trial set out to investigate?

Vincent Thijs (02:22)
All right. The PESTO trial was in response to community members, stroke survivors, wanting to find out whether the current practice of administering Etanercept has done in the U.S. in private practice. In Denmark, I hear there are some sites that provide this treatment. Whether the treatment

and genders can be actually proven according to the standards that we use in the pharmaceutical industry to get it to become accepted as a standard of care treatment. For that, you need to do what we call a randomized controlled clinical trial, preferably two that show evidence that treatment

does what it’s set out to do. And that’s why with this background and the community pressuring the minister several years ago, Mr. Hunt at the time, to fund a trial that would help answer that question.

Design and Objectives of the PESTO Trial

There was a call was set out to do this trial and several groups in Australia

applied and then an independent committee decided to award the trial to the PESTO study group. And then we tried to design this trial to give an answer. So it’s mostly about people that have moderate to severe disability after their stroke that have reduced quality of life. And

We wanted to know, does their quality of life improve when Etanercept is administered? And we wanted to test whether one or two injections were needed.

Because that’s what we heard from stroke survivors that from Australia and internationally that went over to the US. Well, this is how it’s done. You get one or two injections and there was a paper that had shown big effects with one injection. So that was the primary endpoint, but then we also looked at whether two injections could help. And when you design a trial, you have to make a decision, will we focus on people with.

pain after stroke, or will we look at people who have mobility issues or speech issues or cognitive issues? And we saw that current clinical practice actually was people with various impairments after stroke were accepted and received the treatment. And what would have been the advantage of doing say only mobility or only pain? Well, you can then look at the outcome of pain or mobility, does it improve?

Or is your cognition improved? But because we wanted to be pragmatic and we know that recruitment in clinical trials needs to reflect how is current practice. So we thought let’s put in all the people with moderate to severe disability, whatever their impairment after stroke and reduce quality of life. And then we looked at quality of life as an outcome rather than an individual

impairment. And so what we did then was to use the randomized technique and where it’s left up to the computer to decide what treatment a person will receive, the active Etanercept or a similar looking placebo, and then look at 28 days and we had to make a decision what makes sense 28 days, what is practical.

to see whether that injection then had improved quality of life. And then we did another injection again with a placebo or the active drug. And then after 28 days again, we looked again whether that had made a difference. So we have people that had received two times the placebo, one time the placebo, and one active injection. And then we have people that had received two active injections.

And then we were able to compare those and see whether they had made bigger improvements if you receive two injections versus one or zero. Unfortunately, we couldn’t show a difference in quality of life at 28 days. And we also couldn’t show an improvement at 56 days after people had two injections. But that was in a nutshell how we designed and the background of the study.

Bill Gasiamis (07:25)
So the main difference then between the Griffith University study and your particular study was that they did go after a specific improvement in one area, I believe. it in? Okay. So although those guys went after pain, you guys went after just a general improvement in quality of life after the injection and your stroke survivors.

Vincent Thijs (07:39)
Mostly, think.

Bill Gasiamis (07:54)
would have been as far as 15 years post stroke. Is that right?

Vincent Thijs (07:59)
Yes, correct. We wanted to have people early after stroke between one and five years, and then also between people five to 15 years after stroke. That was also for practical reasons. Once you start trial, you see how good recruitment is, how many people want to participate in the study. And we saw that if we went to up to five years.

Recruitment was relatively slow. So we added this additional group of people later on after their stroke. that because many people, I’m five years, I’m six years after stroke. Why can’t I get the treatment? And you know, so we also wanted to expand the pool. And that’s also what happens in clinical practice. Current clinical practice, I don’t think the sites and

the US and they would refuse the patient six years or so. We just wanted to reflect the people that we see on the website going for this treatment.

Bill Gasiamis (09:01)
Yeah, yeah. And then the difference between the Griffith trial and your trial as well was the actual dosage of Etanercept the amount that was in the injection. I do believe that your trial was a 25 milligram injection. And I believe that the Griffith University trial was 25 milligram.

injection to 50 milligram injection.

Vincent Thijs (09:34)
Yeah, we just based on what people told us they received when they went to the clinic, also the other sites and then also 35 milligram was chosen because that’s in the patent for the street.

Bill Gasiamis (09:49)
Okay, I see. So you’re trying to as much as possible mimic what was happening out there in in the private practice

Vincent Thijs (10:00)
We wanted to answer the question, is current clinical practice, is that beneficial? And that’s what sort of what the call was to do a clinical trial in current clinical practice. You can, you have to make decisions, right? And I think this was the most relevant for a stroke survivor.

Bill Gasiamis (10:17)
Now that’s really interesting that stroke survivors were able to twist the arm of a minister to get the funding to begin that process of the trial. How long ago did this actually start?

Vincent Thijs (10:28)
I think it was 2016, 2017 or so. So it takes a while to get the minister and then I think that the trial started in 2019. took a while to complete as well.

Bill Gasiamis (10:43)
Right understood. Okay So then you recruit people they come along and they go through the trial through the particular trial How does that work on the day do they turn up are they admitted? We’ll be back with more of professor face explanation in just a moment But I want to pause here because if you’ve ever felt stuck between hope and uncertainty, you’re not alone When you’re recovering from stroke, you’re constantly making decisions and some decisions feel high stakes, especially when confronting information that’s conflicting.

Recruitment and Methodology of the Trial

In the second half of this conversation, we get into the parts that really help you think clearly. What the trial results do and don’t mean, and why placebo responses matter in blinded research, and how to frame smarter questions before you commit time, money, or energy to any path. If you want to support the podcast and keep these episodes coming,

You can grab my book at recoveryafterstroke.com/book or join the Patreon at patreon.com/recoveryafterstroke All right, back to the episode.

Vincent Thijs (11:51)
All right, so we recruited from a variety of sources. So we had kept a log of people that were interested in this. We had a Facebook post in New Zealand, for instance, where we recruited as well. We had people from the Stroke Clinical Registry that were approached. We had a website and people could register their interest if they were doing a search online to participate in clinical trial.

So the variety of sources and then we have to determine eligibility that was mostly done either via an in-person visit or remotely via telehealth. We tried to get their medical information, what type of stroke they had. And then we also questioned whether they had this modified rank in scale, the disability they had, the impairments they had from their stroke. so then people came.

they were considered eligible, then we scheduled a visit and they would typically come in no overnight stay needed. It was a day procedure that was done. People were then receiving another questionnaire on the day itself to measure their quality of life and other measures like their fatigue levels and how much help they required, etc.

And then we proceeded with the injection, which was done. We had bought a special bed that was able to do the, the, the tilting that was required. So we set the people up, injected and then tilted the table. so, we received the drug. It was prepared independently by the pharmacist. So the pharmacist, they took the drug off the shelf or the made the placebo.

and they made sure it looked exactly alike. So then somebody from the trial team picked it up from the pharmacist. The pharmacist didn’t tell, of course, what it was. And then the administration happened. So the doctor who administered and the participant did not know what they received. So after the procedure, they were left like this for four minutes. And then after four minutes, people could sit up again. And we waited about half an hour.

then we asked them how they were doing, whether there were any adverse reactions, ⁓ and ⁓ then after that half an hour of observation people could go back to their habitual situation. ⁓ it’s a very simple ⁓ procedure to do.

Bill Gasiamis (14:35)
I believe there was a was there 126 participants

Vincent Thijs (14:40)
Yes, 126 people participated. had anticipated a little bit more people to participate. So we had hoped 168, but recruitment fell flat after a while and we were not able to find more people to recruit. So we made a decision and then, you know, these clinical trials, they have some funding ⁓ and they require

the treatment team to be paid, et cetera, and that ran out. So we had to stop at a certain time.

Bill Gasiamis (15:13)
Was the study stopped early because of a decrease in the amount of funding or was there an issue with the funding at some point?

Vincent Thijs (15:23)
Funding ran out. You hire people for a certain amount of years and then you have fewer patients than you anticipate. So you have to stop.

Bill Gasiamis (15:32)
huh, okay. So would that affect the outcome of the trial? Would you say the lack of funding or the lack of the ability to take the trial further?

Vincent Thijs (15:42)
Yeah, well, what we had when you do the trial, when you plan the trial, you say, well, this is what we’re going to expect in terms of efficacy. You have to make a guess and say, well, that many people will have an improvement in quality of life if we give them the placebo and that many people will have an improvement in quality of life with the trial drug. And we had thought that about 11 %

would improve with the placebo based on an earlier study. And then we had to make a guess because nobody had done this type of study on what Etanosap would provide. But reading the report that was published several years ago now, where 90 % of the people reported improvement in their impairments, we thought, well,

Let’s not go for 90%, but a 30 % improvement.

And so that was based on that we needed 168 people to participate in the trial.

So that was what we call the pre-planned sample size estimation, which is a guess.

When we stopped at 126 participants, actually we saw that the results were very different. There was not that 11 % actually in the placebo arm. saw that 58 % of the people also had that improvement and 53 % had it with ethanosab. So our initial guess was very wrong based on

some statistical advanced statistical techniques we have. We have quite a lot of power to estimate whether there was a difference. So I think the trial can provide us an answer. It’s large enough to give us an answer about this particular question. Is current clinical practice in these people with this range after their stroke, does it improve?

quality of life after a month or after two months. I’m not speaking about early improvement, I’m not speaking about six months down the line. We only can decide what we see in this study.

Bill Gasiamis (18:05)
So you have some limitations because you can’t have the funding to test one month, two months, six months, 12 months. You have the funding to basically meet the design of your study and then you can report on that. Now what’s really interesting is that the placebo had such a large result.

PESTO Trial Results and Findings

Vincent Thijs (18:34)
What kind of things were people reporting that improved for the people who had the placebo injection?Look, this is, course, when we were in the blinded phase, when neither myself or my colleagues who did these scales, we were totally blinded. And that’s, remember vividly people saying, it didn’t do anything for me. But then there were also people said that they could see again. And so people that had improvement in sensation.

Some people had improvement in their speech. there were, we, we observed these things, but we didn’t know whether they were active or placebo. And then surprisingly we had some people in whom we thought, they must have had active drug that turned out to have the placebo, but that’s years after, right? Because it takes a little bit of time to accumulate a sufficient number of patients. And we were only reporting and breaking the blind when the trial was finished.

because otherwise you may be biased in all your analysis, et cetera. You don’t want to do that. So you wait until the end of the study to break the blind. And that’s very frustrating for the participants because there were many people that said, I must have had the placebo because it didn’t do anything for me. And there were other people that were, and some people like that, they said, I still want to go to the US.

Bill Gasiamis (19:37)
I see.

Vincent Thijs (19:59)
And please, can you tell me if I received a placebo? And I understand it was terribly frustrating for these participants. But we were very strict. No, we don’t want to break the blind. This is against the rules that you have to adhere to in a clinical trial. And so we didn’t do that. Of course, once the trial was finished, we were able to report the results back to the

the participants. And then there were some people that were very surprised that they had received the active drug. I remember one person vividly who said, you have to tell me now because I’m going. And then I said, hold off, hold off. And then we told them you had twice the active drug. And so they decided not to go anymore. So you see how

From a clinical trial perspective, it’s very important to remain very objective and not being able to see what people have received. From a humane level, of course, I understand it was very important to these people.

Bill Gasiamis (21:02)
Yeah, that’d be difficult. ⁓ And then I imagine that had the placebo not worked and then the tenisept did work, then there would have been people who would have said, well, I’ve received the placebo. It didn’t work for me. Other people received the tenisept. It did work for them. Why can’t I get the tenisept injection now?

Vincent Thijs (21:26)
Yeah, and we also had two people, people that had twice the placebo who noticed an improvement and have told me the improvement is still there.

Bill Gasiamis (21:35)
Wow.

Vincent Thijs (21:36)
So it.

Bill Gasiamis (21:38)
That’s amazing. Now was the.

Vincent Thijs (21:40)
And

often that, and I must tell you, often those were relatively little things that seemed to improve both with the placebo and in the active group. And you see that there are changes in quality of life that people have reported, but it happens as well with the placebo.

Bill Gasiamis (21:58)
Wow. Was the intention of the study that was funded at the very beginning in 2016 by Minister Hunt, was it to determine whether or not this was going to be an effective treatment for people in stroke and therefore to roll it out somehow in the Australian medical system for stroke survivors? What was the thinking for Minister Hunt? Do you know?

Vincent Thijs (22:24)
Of course, I was not involved in that lobbying to the minister or anything, but it was to bring it on a pathway towards regulatory approval. We know that Etanercept is a relatively cheap drug that you can get ⁓ and is approved already for some indications, especially in people with rheumatoid arthritis, the condition of the joints, but it’s not approved for stroke. And to be officially approved and then potentially re-

reimbursed on the PBS. You need to have some trials that have been done such as PESTO. We do different trial phases. One would be a phase two trial and a phase three trial. So phase one is typically in people just to assess the safety and some dosages usually in healthy people. And then a phase two is safety amongst stroke survivors.

and preliminary efficacy. And that’s where PESTO was what we call a phase two B trial. And then a phase three trial would then be a trial in many more participants based usually on the results of a phase two B trial. And then usually when you have a phase three trial and it’s convincing and the authorities may approve such a trial.

Bill Gasiamis (23:46)
So in this case, the phase two B trial, this PESTO trial didn’t find that it’s efficacious. And as a result, there’s not going to be a further trial. Would that be accurate?

Vincent Thijs (23:56)
Well, based on the findings we have in this particular type of ⁓ way of administering in this particular group of people, I don’t think there’s enough evidence to argue for a phase three trial. It may be that you could say, well, we want to focus on pain because that was more promising. Well, you’ll need to do another trial in that condition.

Implications and Future Directions for Research

After stroke or maybe within a year after stroke. I mean, there are other possibilities, but at the moment, current clinical practice type trials, I don’t think there’s enough evidence to move forward with that.

Bill Gasiamis (24:43)
What would the numbers have had to look like for the trial to conclude that there was evidence of efficacy?

Vincent Thijs (24:51)
Well, I think based on what we have now, you would need to design a much, much bigger trial because there was only a 5 % difference between the placebo and the active group. And actually it was in favor of the placebo. So the placebo did a little bit better, not statistically significant. So it could just be by chance, but you would need probably thousands of people.

Bill Gasiamis (25:15)
I see. And I imagine there’s not a lot of excitement about funding something like that by the people who fund these trials.

Vincent Thijs (25:25)
Yes, typically the funders will look at how good is the evidence to pursue this. And if you were a pharmaceutical company on a pathway to development for a drug, you probably would say, well, it looks safe, but it didn’t do what it intended to do. So let’s stop the development of this drug for this indication.

Bill Gasiamis (25:45)
I say so.

I think one of the challenges with the path of administering a TANACEP to stroke survivors is that there seems to be a missing step. And the step to me is determining whether or not somebody is a candidate for a TANACEP. perhaps if we knew more about the stroke survivor, what was actually happening in their particular brain, and we were able to determine some similarities between the people who have had a positive result and we developed a method, then that would make it a lot easier.

to say, well, I’m a stroke survivor. I’d like to have a TANACYPT and then go through a process of determining whether or not I was a candidate rather than just guessing whether I’m a candidate or not and then having to pay money to find out whether in fact I was a candidate.

Vincent Thijs (26:33)
The trial provides a little bit of answers to that. ⁓ You want to identify a marker or a subgroup of people in whom the drug will work particularly well. And so you could look at, and we looked at different things like females versus males, if you’re younger versus older, if you have very severe disability or less severe disability, if you have

diabetes, are you early after your stroke or later? That one to five versus six to 15 category. And we could not identify a group in whom the the drug worked particularly well. Now there’s a caveat when you do a clinical trial, it’s really hard to look at subgroups, especially if your trial is relatively small and the PESTO trial is relatively small. So you have to take this with a grain of salt, but it was nothing really promising.

that we could identify. So probably you need other markers. If you believe in Etanercept as a drug, you would possibly need to look at what are the levels of TNF alpha, the drug, the molecule that actually is targeted. Unfortunately, there’s nothing like readily available to do that. Could it be that people with a…

a stroke in a particular location that would work particularly more than in others, but we don’t have any real way at the moment to do that.

Bill Gasiamis (28:08)
Okay, so we’re assuming that the people who experience an improvement after they’ve had an attempt to shut that the markers of TNF alpha were lower or higher or

Vincent Thijs (28:21)
Well, the theory is that they have a lot higher TNF-alpha. Now, as you know, the premise is Etanercept works by reducing this molecule and we have good evidence that it reduces this molecule in the blood, but we don’t have good evidence that it reduces the levels in the brain. That’s where you want it to be. And one of the difficulties and many scientists that work on the Etanercept and ⁓ have said, look, it doesn’t cross the blood-brain barrier. It doesn’t.

go against the natural defense that we have to protect the brain against substances that could potentially be harmful for the brain or that have a large size. And the Tandacep we know has a large size would not cross the blood-brain barrier. So it doesn’t reach the brain. And many people look at it with relative skepticism that it actually enters the brain.

Bill Gasiamis (29:18)
⁓ And then with regards to rheumatoid arthritis, doesn’t need to cross the blood-brain barrier. It just somehow gets to this, position or the place where inflammation is occurring. TNF-alpha is active and it can easily mitigate the impact that TNF-alpha is causing. In the brain, the brain is protected by the blood-brain barrier and it cannot cross the blood-brain barrier under normal conditions and therefore it can’t get to where the TNF-alpha is.

if there’s any TNF alpha, if inflammation is the issue and it cannot resolve it one way or another. So for some people perhaps it can’t resolve it. Now, I don’t understand about Etanercept a lot. I don’t understand exactly how the molecule works, et cetera. But if it was injected into a blood vessel, is that not something that can occur? And if it was, if it can occur, would that then cross the blood brain barrier?

Vincent Thijs (30:15)
That wouldn’t cause a blood brain barrier, no. You would have to do what we call a lumbar puncture or put a little ⁓ injection into the ventricles and then hope that it would enter the area that is stark where the TNF alpha is elevated. Those experiments have not been done.

Bill Gasiamis (30:17)
Either.

Okay, so a lumbar puncture is probably riskier than…

Vincent Thijs (30:44)
Well, it’s uncomfortable. It’s uncomfortable and we do it to administer drugs if needed. Some people with brain cancer receive it. There are other trials ongoing in certain areas of stroke where it’s done.

Bill Gasiamis (30:58)
Then the difficulty is, and my job here is to report back to the community how they should proceed with Etanercept going forward. Now, I don’t expect you to answer that. However, your study probably gives enough information for people to be able to make an even more informed decision than they did before. Previously, what I think was happening is people, and it still happens every day. And I’ve interviewed a lot of stroke survivors who’ve had

positive results with Etanercept. The challenge is getting interviews with stroke survivors who have had negative results with Etanercept. That is something I haven’t been able to do. So if somebody happens to be watching and listening to this and they have had the Etanercept shots and they didn’t get positive results, please reach out so that we can share a balanced story of what’s happening out there in the community. Would there be a reason for the community to perhaps

begin again to lobby a government or a minister of a government to look at perisponinal tenosept and study it in a different way, like administration via a lumbar puncture.

Conclusions and Final Thoughts

Vincent Thijs (32:08)
I think we need more, probably go back to the drawing table to see whether, because we’re just taking a step back. The idea is that there is inflammation after stroke and we know that there is inflammation after stroke. We don’t, we just don’t know how long it is. We don’t have a good marker. Is it present only for weeks or months after stroke or can it persist for years?

The theory is that it persists for years, but if you look at the actual experiments that have been done, it’s really hard to study in humans because we don’t have good tests. But if you look in animals, it’s also hard to do long-term studies in animals, but nobody has really proven that conclusively that there is still after the stroke causes a scar, that process is still really active.

Is TNF-alpha years after a stroke still present? Yes, it’s present because we use TNF as a transmitter in the brain or a chemical in the brain, but is it still worth reducing its activity? That’s probably, I think, a bigger question that science needs to answer is to understand that all inflammation piece and the time after stroke that it persists in my

Bill Gasiamis (33:35)
Yeah, because it could still be the fact that the person has had brain damage. The particular part of their brain that’s damaged has, for example, taken offline one of their limbs and there is no way to recover that once it’s gone. there is no, there may also be no inflammation ⁓ there. So somebody in that situation receiving Etanercept

wouldn’t get a result even if it was able to cross the blood-brain barrier because the damage is done and that’s the challenge with the brain is once it’s damaged restoring the damaged part is not possible.

Vincent Thijs (34:15)
Yeah, look, after this experience with the PESTA trial, I think we need to work on other avenues and I’m not as hopeful with this based on the data that I have seen.

Bill Gasiamis (34:28)
Yeah

Well, my final question then is, are you planning on exploring inflammation and recovery after stroke with any work that you’re doing in the future? Is there any more of this type of work being done?

Vincent Thijs (34:46)
we’ve just launched a new study, which is not a randomized trial, but it’s trying to get at this common symptom that people have after stroke, which is fatigue and cognitive changes. And one of my post-docs, Dr. Emily Ramech, she’s a physio by background. We just launched what we call the deep phenotyping study after stroke. And we are

looking at young people that have had a stroke up to age 55 and we’re taking them into the scanner. We will do a PET scan that’s looking at inflammation. We’re taking their bloods and looking at markers of inflammation and see how that relates to fatigue after stroke. This is between the first month and the sixth month after stroke.

That will give us a little bit of timeline of inflammation after stroke. It will give us some information about fatigue, which is very common, but I have no plans at the moment to look at ethanocephaly.

Bill Gasiamis (35:53)
Fair enough. I appreciate your time. Thank you so much. All right, well, that brings us back to the end of the episode with Professor Vincent Dease on the PESLO trial results. My hope is that this conversation gives you more clarity, especially if you’re felt caught between personal stories, strong opinions, and a lot of uncertainty. The goal here isn’t to tell you what to do. It’s to help you ask better questions and make decisions with your eyes open alongside

a qualified healthcare professional who knows your situation. If this episode helped you, please do a couple of things. Subscribe on YouTube or follow the podcast on Spotify or Apple. Leave a review if you can. It really helps more stroke survivors find the show. And if you’ve had an experience you’re willing to share respectfully, positive, negative or mixed, add a comment. Those real-world perspectives help community feel less alone.

And if you’d like to support the podcast and keep it going, my book is at recoveryafterstroke.com/book. And you can join the Patreon at patreon.com/recoveryafterstroke. Thanks for being here with me. And remember you’re not alone in this recovery journey.

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