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Episode 67: Finding the Cure
21 Plays25 days ago
In this episode we talk about the promising autoimmune treatments that are in development.
Sources mentioned:
T-Cell Vaccine Studies
DEN‑181 Phase I Trial in Humans
Peptide–MHC Complex Vaccine in Animal Models
Preclinical Peptide-Based Vaccine Studies
Local Anti‑Inflammatory Gene Delivery
Immune tolerance induction with multiepitope peptide
RNAi & Epigenetic Gene Silencing
RNA interference-based gene therapy for successful treatment of rheumatoid arthritis
Probiotics: Strains That Show Promise
Rheumatoid arthritis and the intestinal microbiome: probiotics as a potential therapy
Fecal Microbiota Transplantation (FMT)
Pre-clinical Mouse Study on FMT
Precision Medicine and Biomarker Testing
Stay informed about PrismRA or comparable predictive tests
Clinical Trials Near You
You can search for trials involving new medications, immune therapies, diet studies, and more:
ClinicalTrials.gov (Worldwide)
- Search for “Rheumatoid Arthritis” + your country
- Filter by “recruiting” if you’re interested in taking part
- Includes info on the treatment, who qualifies, and how to apply
Recommended
Transcript
Introduction and Podcast Overview
00:00:00
Speaker
Welcome to the Wounded Healers podcast.
00:00:10
Speaker
I'm Janessa. And I'm Amy. We were brought together by our shared wound of an autoimmune condition in our early 20s. This is a place where we explore our wounds with our listeners and guests who recognize the challenges of being human in hopes of helping all of us let the light in.
00:00:28
Speaker
hi everybody, welcome back to Wounded Healers podcast. We hope you're well.
AI in Health: Chat GPT's Role
00:00:35
Speaker
We hope you enjoyed last week's episode all about, what was it about?
00:00:42
Speaker
Asking chat GPT, yeah, Leveraging AI in helping you understand and deal with your um illness.
00:00:55
Speaker
We've got, yeah, but and it was, go on, please. I'm sorry. ah Yeah. And it was really interesting because along that journey, we figured out that there were some things that are on the front for what could help us in the future.
00:01:10
Speaker
And so Amy had the idea during the episode, as you heard, to let's do an episode on that because that's hopeful. Like we started out the last episode a little dark. It's getting even lighter now. Yay. Yeah. yeah there is hope on the horizon and that's a really fun thing to think about especially when we you know we were all diagnosed with there is no cure and that really makes its mark on you and sticks with you I was thinking just the other day weirdly like what am I like eight years on
00:01:44
Speaker
just how much it sucks to have that kind of hanging over your life you know that you have a disease with no cure it really you can really fall victim to that idea it's really nice that we can say like we're getting closer to a cure in inverted commas they did say that these the treatments we're going to talk about don't really mean a cure but they mean very effective long-term treatment which is basically the same thing as a cure right in my book i'd say as far as i'm concerned yeah yeah
00:02:28
Speaker
okay so should we just get into it you think Yeah, hop right
Innovations in T Cell Vaccines
00:02:33
Speaker
Let's go. Okay, so the first thing we spoke about, and well, it wasn't the first thing we spoke about in the episode, but the first potential cure that we spoke about towards the end of the episode were T cell vaccines. and So these are one of the most exciting areas of research.
00:02:53
Speaker
because they're aiming to do what our current treatments can't, which is retrain our immune systems to stop attacking our joints, and which could potentially lead to a lasting remission or even a cure maybe.
00:03:08
Speaker
say this is how it works and also guys just forgive us because as you know me and janessa are not doctors janessa janessa closer to it than me but um still neither neither of us are um and this is unsurprisingly quite um medically what we're going to talk about obviously we're going to try and simplify it as much as we can yeah for our own benefits as much as yours and But yeah, just bad with us. We're not doctors.
00:03:40
Speaker
Just for any legal purposes, not doctors. Please, you know, take this as just a hopeful ah say on things on the horizon and not as as Bible. Yeah, you're just talking to your arthritis besties and we're just discussing potential things that are coming up.
00:03:57
Speaker
And none of this is none of this constitutes advice. OK, thank you. Yes, covered our bases.
00:04:05
Speaker
So unlike traditional vaccines, which help your immune system attack viruses, T cell vaccines for RA do the opposite.
00:04:16
Speaker
They help the immune system tolerate certain proteins in your joints so it stops attacking them. It's called immune tolerance therapy.
00:04:29
Speaker
So in RA, as we know, the T cells, which are a type of wet white blood cell, they get confused and wrongly identify our own joint tissue as dangerous.
00:04:42
Speaker
That triggers inflammation and recruits other immune cells starting to cascade through our bodies and create a lot of joint damage. So the vaccine, the idea of it is to expose the immune system to a specific piece of the joint protein, an antigen, as a safe, controlled way so that it learns, this is me, this isn't a threat.
00:05:11
Speaker
So it's a bit like giving your immune system a crash course in what not to attack, like teaching it not to overreact. And so this can involve peptide based vaccines, which are tiny protein fragments from joint tissue.
00:05:29
Speaker
DNA vaccines, which are pieces of genetic code that train immune cells, or nanoparticle carriers, which are special delivery systems that present the teaching antigens without triggering inflammation.
00:05:47
Speaker
So all very clever, but I think I understand that. Do you understand that, Janessa? Yeah. That makes sense to me. i I think it's really interesting training your body, like, to be like, that's me.
00:06:00
Speaker
Don't take it away. like Yeah, it is something I would say it's almost as intense as training a dragon in my mind. just being like, okay, you crazy thing here. Please don't attack this anymore. so yeah, that seems like it just honestly, like,
00:06:17
Speaker
really amazing that that's even a possibility that that could happen to like train our bodies that way yeah rev reverse reverse engineering the body yeah um so where is this in development we're in early human trials that's pretty cool phase one and two several versions are being studied in human trials there's one called den one eight one in australia So this is a nanoparticle vaccine delivering RA specific peptides and vitamin D3 to encourage the immune tolerance.
00:06:52
Speaker
Phase one showed that it was safe and had early signs of effectiveness. So that's great. We have the immune tolerance network in the US and the UK, which is just such a thing for America to call.
00:07:08
Speaker
it's treatment yeah This is the immune tolerance network. never now and So this involves research groups running tolerance inducing antigen therapies using peptides like type one collagen or citrullinated vimentin,
00:07:31
Speaker
who knows? Couldn't any better on that. Yep. It's still early, but it's promising. So that's great. No more information on that apart from it's promising. So we love that. um Biovaxies and others. So private biotech companies are developing personalized T cell vaccines for autoimmune diseases using patients' own immune cells.
00:07:53
Speaker
And I think I listened to you another podcast on this. You know, oh my God, Jordan Peterson. You know that guy? He's like really divisive. um Have you heard of him? Jordan Peterson. He's like an older guy. i don't know if I have, but I think you've brought him up before. Yeah, yeah i probably have. yeah His daughter, he's called Malika or like Michaela or something. she has...
00:08:20
Speaker
She had juvenile arthritis and she had a guy on who works at a biotech company talking about these um vaccines. So if I can remember her name and remember her podcast and find the episode, we'll link it in the show notes.
00:08:39
Speaker
Okay, so the caveats to this. Obviously it's still in early stages. It's not yet approved or available outside the clinical trials. Apparently it may only work well early in the disease before too much joint damage occurs. But I mean, i guess that's what you want is just that immediate protection because we know that Early on in the disease is when the most joint damage occurs, when it's not under control.
00:09:08
Speaker
um We don't yet know how long the effects will last. Repeat dosing may be needed, which is okay because we are already we're all already on repeat doses of everything anyway. so yeah yeah So this is hopeful because this research is part of a shift from controlling symptoms to reprogramming the disease, of course.
00:09:31
Speaker
um It's not science fiction, people. It's real with funded trials in early human participants. and So what to look out for if you want to keep up to date with the T cell vaccine research. um There are obviously these ongoing clinical trials.
Exploring Gene Therapy Potential
00:09:50
Speaker
DEN 181 in Australia likely entering phase two. So we can expect data on FD. I don't even know what that word is.
00:10:01
Speaker
Oh, cringing. What does this mean? um effica Efficacy. Oh, that's just efficacy. Great. Okay, yeah. I think so. Great.
00:10:11
Speaker
We got this, guys. Okay, we can expect data on efficacy. and
00:10:21
Speaker
Yeah, we might see some more and human testing coming up on the other ones as well. And at the end of this, we can actually talk about how to sign up for clinical trials.
00:10:33
Speaker
Not that we're encouraging you to do that, but... there are links and websites and stuff where if you're interested in doing so, you can sign up. And I pre-looked those ones across the UK and there's ones across the States as well. I mean, they're actually worldwide. So if you feel like being a little guinea pig or mice, if you feel like taking over from the poor mice, ah we'll let you know at the end about where you can do that.
00:10:58
Speaker
Oh, so cool. All right. So the next one we're going to talk about is more of like ah again, kind of like gene therapy for rheumatoid arthritis. And similar to what we just heard, the idea is to reprogram the immune system. And in this case, it's silencing or correcting faulty responses that cause your own joints to be attacked.
00:11:16
Speaker
um Pretty much what we know to be rheumatoid arthritis. But the second one is called local anti-inflammatory gene delivery. That's a mouthful. But how exciting. So it uses viral vectors. And then it says, you know, which are AAVs.
00:11:32
Speaker
um Don't know what that means, that's just stick in here and we'll find out. So these are injected directly into your joints to express anti-inflammatory proteins like IL-10 or TNF inhibitors, but only when needed and avoiding system systematic, woo, effects.
00:11:49
Speaker
So that's interesting. So these are gonna go right into the joint. That can be painful, but if it helps, if it makes me better. I'm all in for it. So the benefits of this, what could help us make make us feel better is it's a localized therapy.
00:12:06
Speaker
So it's going right into the joint and it's avoiding the entire immune system suppression, which is going to be so helpful for us, especially with like colds. And I know if you went through COVID, you know.
00:12:17
Speaker
With RA, that was a scary time if you were on immunosuppressants. So this could be something that's really hopeful. So the status of this so far, it's still in animal models, which I believe is referring to the animal studies as well.
00:12:33
Speaker
And so it's safety and ethical studies are underway, ah but they still have to be tested and proven before moving on to humans. So in the real world, caution.
00:12:46
Speaker
And so i love this. um You guys, we got this from Gpt, chat Gpt, and this is so funny to just read out loud. So here are those real world cautions. So past gene therapy trials are what we're going to focus on. And so the first one of these was in the early 2000s. It was a trial that used the AAV to block TNF production.
00:13:07
Speaker
And unfortunately, a fatal fungal infection occurred in one of the participants taking Humira as well. So you guys, that is, let's take a deep breath together. It's going to okay. Imagine dying of a fungal infection.
00:13:22
Speaker
ah Yeah, that is really rough. And and thank you to the queen or the king that did that for us so that we have that information. like man, you know, you guys, we just have to take a moment to see the parallels between being cave people and this. Like, yeah who's going to eat the berry first and show whole tribe if we can eat this? Like,
00:13:38
Speaker
Truly respect to that person. The other thing about the trial is the trial underscored the need for extreme caution with systematic suppression um and reinforced a strict safety protocol. So again, that person passing is really tragic. There's no way around that. But it did have the silver lining of making it more cautious.
00:14:00
Speaker
So that will show areas that maybe the people studying it didn't take into consideration as much before. So again, that immunosuppression is really important. OK, so you guys, the next thing we're going to talk about is RNAi, which sounds like some weird form of ai But it's called RNAi and epigenetic gene silencing.
00:14:23
Speaker
So RNA is an interference. RNAi delivers small RNAs to silence the genes, driving inflammatory responses into our joint cells.
00:14:34
Speaker
And this is seen as a promising study, which is pretty interesting. um this is interesting to me because this almost kind of reminds me of what the biologics aim to do at this point which is to encode with your dna to encode for inflm inflammation as if you've already processed that so that's interesting that sounds like it's along the lines too of what some biologics aim to do and then the other thing is the epigenetic approach so that's an aim to adjust the gene expression in the joint immune cells
00:15:05
Speaker
And that will alter the DNA methylation or histone modifications, mostly theoretical now. So that's interesting. So epigenetics, you guys, and that epi means above and genetics is your genes.
00:15:19
Speaker
So these are factors that are above our gene encoding that impact our gene encoding. So for example, that would be like environmental stress and or if you ate something poisonous and your body responded to that.
00:15:32
Speaker
It's anything that's outside of your genes that's impacting them to encode differently. So I think that's really, really cool. um And I've always been interested in epigenetic. I think there's just so much information there.
00:15:46
Speaker
Yeah. yeah And then the next gen RNA viral delivery innovations. um just so we have a little taste of that, is that researchers are working on safer non-viral nano nanoparticles, circular ah RNA therapy, and better targeted gene carriers to reduce side effects and off-target risks.
00:16:09
Speaker
So that was a mouthful, but just know people are working on it. They're doing their best out there. And the challenges and risks that are involved is the delivery accuracy. So just making sure that you know each gene or the gene reaches only where they're needed. So that's something important. I think what we saw with that kind of terrifying news that someone did pass is like there has to be accuracy in it being delivered right where it needs to be.
00:16:35
Speaker
And then again, safety, safety, safety. So avoiding any systematic effect and infection risk, again, noted with that. king or queen who took took one for the team.
00:16:46
Speaker
um Durability is definitely necessary, and that's just ensuring that there's lasting benefits without repeated dosings, which is interesting because, man, wouldn't that be nice? You'd go like once or maybe twice, and there you go That'd be cool.
00:17:02
Speaker
um Clinical maturity. So most approaches are still in animal or early stages of research, so no FDA approval yet. um for gene therapy for RA. So again, this is just on the horizon. You can just continue to stay informed with those, which we'll put in the show notes. And again, Amy did say that some of these are actually looking for volunteers. And after we read that very terrifying section,
00:17:28
Speaker
ah we want you to know that we're not saying you should volunteer or you shouldn't that it's your individual choice again yeah so yeah you guys that that is yeah I say stay away from this one to be honest it yeah I would feel like that one yeah I think leave but leave the local anti-inflammatory gene delivery to someone else I don't want any of our listeners getting involved in that to be honest we'll just we'll just take the benefit when it comes when it comes yes okay the next one is ah so i'm i'm I'm now dying because i actually have come to realize that talking about probiotics might even be harder to pronounce than some of the gene things.
Gut Microbiome and Immunity
00:18:13
Speaker
and but it's I'm going to talk to you about um ah recent gut microbiome research, which is exploring and specific probiotics and fecal transplants as tools to influence immune balance in rheumatoid arthritis. So honestly, this makes me happy and excited because I feel like it's more along the natural, um holistic solutions. like
00:18:46
Speaker
especially the fecal matter transplant, you know, like that is literally recycling, no? So we love that. Reduce reuse.
00:18:58
Speaker
And just imagine, well, I'm sure we'll get into it, but like, just imagine if, you know how we have like the donor list of like when people need a kidney, imagine it's like donor list of your feces. Your feces.
00:19:12
Speaker
Yeah. your um your feces are a match to someone and for the rest of your life you just like send away your turds to wow i mean that's amazing it's impressive i'm sure that that's not what's gonna happen but um okay so a 2024 review highlighted several strains of probiotics with anti-inflammatory effects in both animal and human studies.
00:19:41
Speaker
um Lactobacillus casei, which this is, that's a mainstream one. I've heard that, like they've literally said that on adverts. In an eight week RCT, it significantly reduced pro-inflammatory markers and increased IL-10.
00:20:03
Speaker
don't know what that is, I think we might have mentioned earlier. um So it improved disease activity scores. So that's promising. Let me just find out what IL-10 is right now, if we can, so we're not leaving the people hanging.
00:20:18
Speaker
Okay, it's interleukin, a pleo, oh my God, a pleotropic disease. tropic cytokine meaning it has various effects on the immune system it's primari primarily known for its potent anti-inflammatory properties playing a crucial role in regulating the immune system and preventing inflammation um okay so let's just assume it's a cell or something anyway so lactobacillus
00:20:51
Speaker
K-Sci was good, increased something calming and soothing in our bodies, reduced pro-inflammatory markers and improved disease activity scores. so Perfect. And then there's L-Rhaminosis and L-Ruteri, which improved health assessment questionnaire scores and reached something response in active ah r RA patients oh god can you guys can you tell we have just like busy lives and we don't really we don't really research this episode before we started and it's it's been real it's been really all
00:21:28
Speaker
We've been having a crazy time. We've both been having a crazy time at the moment. um So the ACR20 response criteria was developed by the American College of Rheumatology and it's a standard way to measure improvement in rheumatoid arthritis clinical trials.
00:21:42
Speaker
There you go. um It requires a 20% improvement in both tender and swollen joint counts as well as a 20% improvement in at least three out of five additional measures. Okay, so that that's just a scale.
00:21:55
Speaker
So they those strains of bacteria improved scores. So that's great. Then we have bifidobacterium strains. And in animal models, they reduced arthritis arthritis symptoms, bone damage, and inflammation, while also rebalancing gut flora.
00:22:15
Speaker
We love killing two birds with one stone. and Feed two birds with one scone. Have you heard that one? No. I'm sorry, I heard that recently and I was like, I'm totally gonna use that. That sounds very British. Did you hear that somewhere to do with British British?
00:22:33
Speaker
No, I didn't, but heard someone say it and i was like, I'm gonna steal that. That's coming with me.
00:22:40
Speaker
um And then Basilius Coagulens, guys, I'm sorry. 60 day RCT showed meaningful reductions in pain scores and improved mobility compared to the placebo.
00:22:55
Speaker
So that's good. So probiotics can decrease inflammatory markers, boost anti-inflammatory IL-10 and help restore gut microbiome balance. Meta analysis of ATRCTs in inflammatory arthritis found modest clinical improvements and minimal side effects like mild GI upset.
00:23:17
Speaker
So that sounds good. Again, like I was saying earlier, it's appealing that it's, you know, something natural. It's, I guess, I think it's not like pumping loads of chemicals into your body that have negative side effects.
00:23:31
Speaker
But I will say equally, the results don't sound as like concrete as some of the other stuff we spoke about. It doesn't sound like they can actually illustrate.
00:23:44
Speaker
um healing it's just people well significantly reduced plurian inflammatory markers i guess that is clinically demonstrating healing isn't it yeah it is but i hear what you're saying it doesn't have that kind of vava voom that everything else has and that like promise of like yeah i'll be great you're like oh good yeah you know this one's kind of like it'll take a lot of time and slowly these markers will lower yeah and it also sounds like those markers could shoot back up at any time which is we we know to be true with RA.
00:24:14
Speaker
um Okay, the fecal microbiota transplantation, f m t is showing early signals in r RA.
00:24:26
Speaker
So while FMT is well established for treating C difficile, its potential in RA is still emerging. There's been a single case report in 2020, which described a patient with refractory RA who experienced symptomatic improvement after MFT.
00:24:47
Speaker
um So that's promising, but those results need broader validation. Preclinical mouse models showed that FMT from RA patients induced depressive-like behavior and systemic inflammation via T cell changes suggesting that microbial imbalance can influence disease and mood i'm so sorry we made mice suffer depression oh yeah dude firstly i'm like it is horrifying how do they even diagnose a mouth of depression
00:25:26
Speaker
I don't even know. It just is like not on the wheel anymore. I'm a little hamster wheel. It's just in the corner. just looking at the wall. um I have no clue. That's sad though. But honestly, it's really interesting because everything that has to do with your gut, like your gut produces the majority of your hormones in your body. I think we forget that. And like if this is going in, um ah my my thing I imagine is if the fecal transplant, if the the donor is not like actually that well in their flora then it could just put yours so off balance that it could like trigger a different kind of hormonal response so that's like a little terrifying but honestly to me just as terrifying as as other aspects of like clinical things yeah um but it does kind of you know go back to like
00:26:17
Speaker
how but will they find these people because you'd almost have to be like a kid to not have your gut flora be that off balance you know so like this would be like someone who rarely uses antibiotics who eats a very balanced meal who has a really balanced flora and like that is so hard to find yeah it's hard to find and i guess those principles you Correct me if I'm wrong, but I guess there's principles where we can attempt to deliver that to our own systems without the need of a transplant from someone healthy, right?
00:26:55
Speaker
Like trying to restore our own gut barrier integrity. I see what you're saying. yeah Yeah. So there, there's a lot you can do on your end through pre and probiotics. Um, however, there are some floras that once they fully die out in your system, they're very, very difficult to reintroduce.
00:27:15
Speaker
Um, and those are like really extreme cases, like someone who is on antibiotics for a very long time for like a staph infection, like something, something really out there. To which if that's you, I apologize. That is a really rough thing to go through.
00:27:28
Speaker
um But yeah, so I think as long as you haven't completely eradicated a specific type of gut flora, then you can hopefully bring it back and flourish it using gut flora.
00:27:41
Speaker
proper probiotics okay yeah cool um so as well as restoring gut barrier integrity what's also at play when it comes to this kind of therapy is that it increases short chain fatty acids which promote healthy regulatory c t cells which we heard about earlier so maybe something you can do there as well And also they work by modulating immune signaling pathways to dampen autoimmunity.
00:28:14
Speaker
i So in terms of clinical takeaway from this, most evidence remains preliminary. Some small scale RCTs and animal studies.
00:28:26
Speaker
The things we spoke about earlier, so the L-rhaminosus and the most consistently studied and safest options in RA.
00:28:46
Speaker
So, I mean, goes without saying, it can't hurt to just throw some probiotics into your supplement mix. Again, not a doctor. So don't just start doing that. Do your own research. But um we have a sponsor. We have a code. We Yeah, we do.
00:29:03
Speaker
Yeah. We'll put it in here um as soon in a second. You'll hear that run. Yeah. If you think you can trust anything either of us have said to you today from the way that we have like blathered our way through it. But yeah, we'll throw our advert in so you can use that code.
00:29:22
Speaker
Hey there, healers. We're going to take a quick break to introduce you to some of our sponsors. Hey healers, it's Janessa and I'm here to remind you about Just Thrive, which is a pre and probiotic brand. We spoke of them briefly on our nutrition episode, but I'm here to remind you because after getting certified in nutrition, I found that a hot topic was pre and probiotics.
00:29:41
Speaker
Now, unfortunately, research shows 95% of probiotics don't even make it to your digestive system, which is where they're needed most to help our flora and fauna. Thankfully, Just Thrive has created a product that does just that.
00:29:52
Speaker
It just thrives. So it makes it all the way to your gut in support of your flora and fauna. And let me tell you, i have seen a huge difference since I started using their products. In fact, so much that I reached out to them and said, can we please, please get a promo code for our listeners?
00:30:05
Speaker
And they said yes. So they've hooked us up with a 15% off promo code. which is WHP. Again, that's WHP for Wounded Healers Podcast. You can put that in on their website for any of their products to receive 15% off.
00:30:19
Speaker
Thanks so much, listeners, and continue to lit the light in. Yeah, and look it up too. That's the other thing. i know i'm I'm someone who's always like, even if I love somebody, I'm going to do my own research like no matter what and just make sure it's on par for me. So just do that. Don't just take our word for it. Look at their website. Look at their third-party testing. Yeah.
00:30:39
Speaker
take a peeky peek it's it's some good stuff yeah and also discuss probiotic therapy with your rheumatologist and get some actual qualified advice on what would work best for you what would work best in relation to all of the current treatments that you're on i feel like honestly sadly a lot of rheumatologists if you're like can we have a discussion about probiotic therapy they would like laugh in your face i know my personal rheumatologist would be like shut up ah No, he wouldn't tell me to shut up, but he would kind of like laugh it off and be like, that's nonsense, sadly.
00:31:12
Speaker
But um if you have a progressive rheumatologist, then definitely, yeah definitely discuss with them. Yeah. Yeah, nothing out there for sure. I guess in the, well, I guess I do.
00:31:25
Speaker
In the US, most doctors are not required to take nutrition for more than two hours as a part of their doctorate program. So just, you know, just know if a doctor does try to tell you nutrition has nothing to do with what you're going through, make sure to do your own research too, because they're not incorrect from what they learned. It's just, they didn't learn much of it.
00:31:46
Speaker
So there's always other avenues. You can look like dieticians who are registered. um I would focus on that, especially if you have an autoimmune disease to see someone who went to college and became a dietician for that. Yeah.
00:31:58
Speaker
Cool. Okay. Back over to Janessa to talk about something extra exciting. Yes. Okay. So we're going to talk about precision medicine and biomarker testing.
00:32:10
Speaker
um So this is why it matters. So RA treatment today often involves trial and error, as we just heard. And starting with methotrexate. Oh my gosh, you guys help. methotrexate And then switching to biologics or JAK inhibitors if it doesn't work.
00:32:26
Speaker
So this process can drag on for months and even years, increasing cost, side effects, and joint damage. You guys, OK, hello. We're both raising our hands here. Amy and I are like us, us, us.
00:32:37
Speaker
Yeah, we, a lot of us know the trial and error, error, error, the error's tour of trials. Anyway. um My medicine error's tour. The methotrexate error. Yeah. Yeah.
00:32:48
Speaker
My mother, Drexate 1, would be like, ow, ow. So yeah, we we all know how this goes. Truly, I think that is the most understandable thing. So like it's got me hooked. and So precision medicine, so it aims to predict which drug will work best for you up front.
00:33:05
Speaker
And we talked about this in the previous episode. Amy brought this up, and I had never heard of this and was like, oh my gosh, that's a dream. So the idea is using a biological signature in your blood, um synovium or gut.
00:33:19
Speaker
So that's how it would work. And so the biomarker method development is using the synovial tissue for profiling. So it's single cell and spatial transmissions.
00:33:31
Speaker
crypto Cryptomic, I believe that's pronounced, studies show that RA joints fall into distinct pathotypes like fibroblastic rich versus immune cell rich synovium.
00:33:43
Speaker
So that's a mouthful and ah very interesting. But these types respond differently to different drugs. So TNF inhibitors, rituxim, as we heard. Hey, rituxim. I was on that. You guys, that was an eight-hour infusion, like, once a month. That was eight hours in a chair. I was like, whoa.
00:34:01
Speaker
Anyway, um it it decreases the more you're on it to, like, five hours. But anyway. So I i ah will continue. So biopsy driven trials for this. um And it's telling me that that is called the Humby and et al.
00:34:18
Speaker
I don't know. Sounds interesting. Are already using this to choose therapy. So people are starting to use this. That's interesting. So blood-based biomarker panels. So that's another aspect of this. So the multi multi-biomarker disease activity, which they're referring to as MBDA, tests combined markers like CRP, IL-6, TNF-R1, MMP-3. Okay.
00:34:43
Speaker
sort dash three ah okay and for example a 24 marker serum panel predicts the response to and crep in creptic and creptic oh man and uh i think that's and that's it that's one of the drugs that's one of the drugs really okay this i cannot pronounce that one yeah it's they it's It's a medication that works by blocking the effects of a protein called TNF alpha, which is involved in and inflammation. It's used to treat various immune conditions.
00:35:16
Speaker
So what what's that saying is it's these blood-based biomarker panels have already been used to successfully predict response to Entracept with 58 to 72% accuracy. That's pretty good. 72? That's pretty accurate, yeah.
00:35:36
Speaker
I'll take that. Anyway, so machine learning tools for Prism RA to integrate gene expression, ah SNPS, and clinical features to forecast the TNFI responsiveness.
Biomarkers and Emotional Impact
00:35:48
Speaker
We'll link that in the show notes. If you're interested in seeing more of that, that's going to go into like very big detail on that. But we're go to move on to the omics integration. um So genomics plus transcriptics and microbiome. So multi-omics analysis, which is blood RNA genetics microbiome composition, have successfully distinguished responders versus non-responders to methotrexate and biologics.
00:36:16
Speaker
So that's interesting. Wow. Were you a responder to methotrexate, Amy? I mean, I think I know this. Yeah. Yeah. Never mind. No, I was. um I was just not initially. I guess this isn't saying that they can tell you what dose, but that was the thing with me because obviously they start you on a not as um high dose and that did nothing. And so that it was just a long...
00:36:40
Speaker
time until eventually got i got up to whatever is the maximum you can have orally which was like 25 so I like I started was like 10 went up to 15 went up to 20 went up to 25 so it felt unsuccessful um because it took so long to increase the dose to something that actually calmed my disease and I guess this isn't saying that it can tell you and how much you should take but still like if i know there's many people that have taken methotrexate and it hasn't worked so if you can just skip methotrexate altogether that's going to be going to save people a lot of time and discomfort
00:37:22
Speaker
Yeah, yeah, absolutely. Because I do remember at one point I felt like I was having a hangover off of trip. Oh, yeah. The next day I'd wake up and I was like, oh, every every Thursday used to be my my like a plant hangover with no fun. and like Just the the effect of it. Yeah.
00:37:40
Speaker
ah Well, as we continue on here, so 2022, review cited baseline gut microbiome differences and blood transcriptome profiles as promising predictors. And again, we'll link that. So that's just more information on those predictors and how this will work.
00:37:57
Speaker
So how accurate is it so far? Again, we got a little bit of a percentage up there that they were basing part of this off of another medication. But conventional markers, RF, ACPA, offer limited prediction and composite panels of MBDA, prism RA, and synovial pathotypes show better performance but need validation in border studies.
00:38:20
Speaker
but Border, you guys, broader. I'm so sorry. Broader studies. So we just need to expand more on those. And then synovial biopsy are promising but invasive and not yet routine, though biopsy-driven trials are showing proof of concept.
00:38:36
Speaker
So that would be really, I wonder how they, I'm interested in how they do that. Because if you've had your, um like your joint, oh my gosh, the word is escaping me, aspirated.
00:38:49
Speaker
If you've had your joint aspirated, which means they pull out the synovial fluid that's just sitting there not able to move and your body's not processing it. You see this like humongo syringe of synovial fluid. And I wonder if that's what they're talking about for that bile. Yeah, no idea, but I'll have to look into that more. They do, I just looked it up. It's a blind needle biopsy. So a needle is inserted directly into the joint to collect a sample, you often used for larger joints like the knee.
00:39:16
Speaker
Or they can do an arthroscopic biopsy, which is an arthroscope. So a small camera is inserted into the joint to visualize and allow for tissue sampling using a biopsy tool. Jesus.
00:39:31
Speaker
Yeah. ultrasound guided needle biopsy that's something that I nearly had but then they decided my my finger was just broken um but ultrasound ultrasound imaging guides the needle to the tissue allowing for precise and controlled sampling so all much of a matchness but it's basically harvesting with a needle yeah wow oh yeah yeah I had that that done on my knees quite a few times and it felt so good once they took out the synovial fluid yes For like two days, I was like, I'm cruising.
00:40:05
Speaker
Okay, so what this means for us. So um again, I think we've kind of reiterated this, but I'll just quickly go through it. but But this means it's more tailored treatments, of course, kind of like choosing a biologic or a JAK inhibitor.
00:40:19
Speaker
And based on your biomarkers could get you to remission faster, which is like, yes, please. And then fewer unnecessary side effects. We talked about that. Amy brought that up with methotrexate.
00:40:30
Speaker
And it avoids joint damage, which I think that goes without saying is we're trying to do that more effectively and faster. and i ah I'm going to go ahead. ah iaac I just want to add one on. I want to add one on here. i want to add a number four because i think they're really missing that it will save you a lot of...
00:40:50
Speaker
emotional trauma slash heartbreak slash a mental load that we that we suffer with at the beginning like that and that could be just as impactful as having finding out the right treatment for you because it's like that on i'd say it's not really unspoken but it's not unspoken we within the community talk about it but on the outside people don't talk about the the mental degradation that you suffer when you're trying to land on a treatment that works for you and feel like yourself again so this could save a lot of that for patients yeah oh that just reminds me too of when we had Vanessa on for an episode as a guest she mentioned ah like we were talking about something and she was like yeah that's medical trauma and I had not ever considered that really um which is really funny for me because I feel like I would be aware of that but I was like oh my gosh you're right just kind of worrying how like
00:41:50
Speaker
everything is going to work or like if you're going to feel like cred again or like if you're going switched again that's all yeah really medical trauma truly so what you're saying is so valid amy like how do we avoid that kind of trauma where where you we feel like when we walk into an office we're just gonna hear we're gonna get switched to another thing or yeah bad side effects or whatnot yeah oh yeah So there is a WhatsApp section for what's next. Big M will link those. i am There's some actionable steps ah here for this. And you can, of course, like we mentioned, you can talk to a rheumatologist about this so that they can offer MBDA or similar tests to track disease activity.
00:42:32
Speaker
Watch out for clinical trials, which are linked below. um And they'll offer clinics offering like synovial pathotyping so that's interesting stay informed about prism ra for comparable predictive tests that are coming up and yeah we'll get those links below yeah and so i think that was a lot of info so if you're like what the what know that you're not alone but at the same time at the same time you guys it is like
00:43:05
Speaker
in a good way, a lot of info because it's like, okay, these are a lot of things on the horizon. like yeah literally I, I learned and I don't know if, if they talked to you about this, but Amy, when I was first diagnosed by first rheumatologist who absolutely loved her, she mentioned that way back in the day. So like, and I want to place this in like I can't place it. I'm going to do wrong.
00:43:27
Speaker
But way back in the day, they would inject gold into people's joints. Wow. Because they believed that that could like alchemize and change the joint.
00:43:38
Speaker
So meanwhile, they were like straight up like making people even more sick. Yeah. But this was like right when we started to understand RA, like not even understand, but like to put a name to it. So just knowing something was going on. So that one point they were just injecting gold.
00:43:54
Speaker
So you guys, we've come so far. Yeah. So far. Yeah. like Wow. Yeah. That's epic. I think a quick recap for anyone who can't even remember what we talked about at the start of this episode, because I think if I was listening, i also wouldn't be be able to remember.
00:44:11
Speaker
So it was cell vaccines, which is retraining your immune system. So it doesn't think that the synovial fluid cells are bad. That was one of them. The next one was the anti-inflammatory gene delivery.
00:44:25
Speaker
So that was using viral vectors directly in your joints to express anti-inflammatory proteins. And the benefit of that is that it's localized therapy. So avoids disrupting your whole immune system.
00:44:41
Speaker
The other one we spoke about was probiotics. So they're develop they're working on seeing if probiotics can be strong enough to suppress all of the inflammation markers on their own.
00:44:56
Speaker
We also spoke about fecal metatransplants, which is all about rebuilding your gut barrier integrity from donor feces.
00:45:07
Speaker
And i've And then the last one we spoke about was and using biomarkers to test which medicines are going to work for you faster. So those little quick revision notes.
00:45:24
Speaker
And then I also just wanted to say, if anyone is interested in doing clinical trials, you can literally go on clinicaltrials.gov. And this is a worldwide, it's an American website, but it covers the whole world.
00:45:38
Speaker
You can just search rheumatoid arthritis and your country, filter by recruiting, and it will just list all the trials that are going on who qualifies and how to apply if you want to yeah could be fun I just thought mention that verbally because I know a lot of people don't bother like checking the show notes or following up but I think it could be really fun if you're in a if you're in a position to like do that then you should and also I think you can get you can get paid yeah want everyone to get paid yes get paid get your money baby
00:46:18
Speaker
Yep, it's true. i This is so random, but also really funny. My grandma's in a medical trial for a hearing aid. And it's so cute. I'm sorry, that maniacal laugh. She's the cutest thing ever.
00:46:31
Speaker
um But she shows me this little hearing aid, the doodad that she puts in. And it's like part of a clinical trial. But she's like, I got this for free. I can hear it for free. And like... She just has to go in and they have to talk to her and she has to make sure it's all so working. That's nice. Because, you know, hearing aids are actually wildly expensive. So expensive. Yeah. Yeah. I was like, what the fork? Are you serious? like Yeah.
00:46:55
Speaker
Yeah. so Yeah. All right. Jess's grandma can do it. We can can do it. you guys can do it. And yeah, ah that was fun. I hope insightful.
00:47:07
Speaker
i apologize again us talking about things we have no idea about, that's just us. Yeah, we're just ahead of our time. I'm just kidding.
00:47:18
Speaker
maybe we're just like yeah we're just trying to understand yeah we're just doing our best just like you guys know best we're just looking forward to cure like you guys yeah so but yeah well you guys it's gonna be two more weeks until we see you back here again but until then we just wish you all well and just please remember to let the light in don't mess that up sorry fine no fine Okay, okay.
00:47:48
Speaker
Yay. Bye, guys. Bye.