ME/CFS breakthroughs: are treatments getting closer?

Vicky Whittemore (0:02): Our goal really was what researchers needed to get to those clinical trials that will make a difference in people's lives.

Amy Rochlin (0:10): There has been incredible scientific work being done in ME/CFS, but we need to organize it and pull it into the clinic and understand who can be helped.

Steve Gardner (0:22): I think we hit a transformational point.

Sonya Chowdhury (0:28): You need that diversity of perspective and technique and technology.

Tahlia Ruschioni (0:34): It is happening and I can really start to feel it now.

Emily Kate Stephens (0:40): Welcome to Make Visible, the podcast shining light on complex chronic illness. I am your host Emily Kate Stephens.

Emily Kate Stephens (1:02): Welcome to another episode of Make Visible. Welcome, Gez. How you doing?

Gez Medinger (1:06): I haven't melted, but it's been a close run thing, and I'm sure many of our listeners, if they're based in the UK or Europe, will have been experiencing similar things over the last week or two.

Emily Kate Stephens (1:16): Yeah, and we are considerably hotter, I believe, right now than the USA. For the people on this side, we are definitely suffering, and it is a theme with these conditions that there does seem to be a definite knock from the heat.

Gez Medinger (1:29): It's twofold. First of all, there's the dysautonomia that results from the heat during the day, but then there's also the impact on being able to sleep when sleep is so critical. There's such a struggle to reach deep sleep in complex chronic illness and heat is one of the things that makes it particularly difficult for the body to settle into deep sleep. So we're getting even less deep sleep than usual, which is already not very much, and we'll often feel particularly symptomatic during the days following.

Emily Kate Stephens (2:07): So, keep cool people.

Gez Medinger (2:09): My top tip: get a towel, put it under the cold tap, then wring it out so it's just damp and cold, and put it around your neck during the day, and have it on your body somewhere in bed during the night with a fan. It makes the most unbelievable difference to keeping your body temperature down.

Emily Kate Stephens (2:29): Fabulous, I'm going to try it.

Emily Kate Stephens (2:31): So we had a really good reception to the overview of Long Covid that we did, and so I wanted to do similarly for our ME/CFS community. We have spoken to multiple different people working in this field to give an overview of where we are in terms of the science of ME/CFS, how that reflects for patients, and where we are in terms of treatment and management of the condition.

Emily Kate Stephens (3:38): I'm going to start with an interview with Dr. Vicky Whittemore. She is a program director at the National Institute of Neurological Disorders and Stroke at the NIH in the USA. She oversees the grant portfolio for ME/CFS and has been a driving force behind the NIH creating a roadmap for ME/CFS research.

Vicky Whittemore (4:17): Our first effort was around 2017-2018. We had a working group that focused on infrastructure needs — training, support for clinical fellows, setting up the biobank, and data sharing. One recommendation was that we needed a research roadmap. That second part was completed a year or more ago. It was meant to look at where the research gaps are, and what we need to know to identify treatments and get to clinical trials. Our goal was what researchers needed to get to those clinical trials that will make a difference in people's lives.

Emily Kate Stephens (5:27): I've heard you saying we have to know what do we know, what don't we know, and what do we need to know — establishing the big gaps in our knowledge and in our strategies. That was 2024, and it's a huge document. I'll point people to it. Would you be able to delve into those primary focus areas so that those listening who are suffering with ME/CFS can understand the direction we're trying to move in?

Vicky Whittemore (6:39): We had eight different working groups and it was impossible to get them to focus on just one or two priorities. But in my mind, the three primary areas are: first, genetics. Within the last several months there's been a phenomenal amount of information coming out from the DecodeME study in the UK. It's likely a number of genes, not one gene, and how those findings can help identify treatment targets. The disease is so heterogeneous — we're going to have to understand each person's private genetic makeup to know what the best treatment is for them. That leads to understanding how genetic makeup impacts dysfunction in the nervous system — brain fog and other symptoms — as well as what's happening in the immune system.

Emily Kate Stephens (8:49): That's absolutely fascinating. So you think a differing gene could lead to a different symptom set. The belief is that many genes lead to a susceptibility — it doesn't automatically mean you get ME/CFS, but a trigger, be it an infection or a trauma to the body, could lead that genetic makeup into ME/CFS. And different genes might lead to different types of ME/CFS?

Vicky Whittemore (9:53): Right. It's polygenic — multiple genes potentially involved — but there is some trigger, because many of us probably have some of those same gene changes but never develop the disease. I think it's the unique combination of the genes plus an infectious trigger that starts you down that road. For most people, it is an infectious disease they just don't recover from, and that hit to the immune system sets you on a path where your immune system just can't cope and can't recover, which then leads to many of the other symptoms.

Vicky Whittemore (10:59): The second area — being in the Neurological Institute, that's one of my prime interests. There's really compelling data showing significant inflammation, not just in the brain but throughout the body. Michelle James at Stanford has amazing work with whole body imaging that shows inflammation throughout. I'm very interested in how the brain becomes inflamed and how we could reverse that — how would reversing brain inflammation impact brain fog and other neurological symptoms? The immune cells are reacting to a trigger, and there is a phenomenon called T cell exhaustion, where one type of immune cell is really trying to react but can't, leading to ongoing irritation and inflammation.

Emily Kate Stephens (12:36): I've heard you express frustration that investigators were looking at B cells, T cells, and auto-antibodies in isolation with no cohesion tying it together. How is that now being addressed in terms of your grant portfolio?

Vicky Whittemore (13:15): Research through the National Institute of Allergy and Infectious Disease is more coordinated now. There's much more open discussion and collaboration — people studying different parts of the immune system are coming together, not only working in different parts but replicating each other's work. Dr. Nath is interested in what comes first — the infection and immune response, and then what happens down the road to involve all these other parts of the immune system and affect other parts of the body.

Emily Kate Stephens (14:21): Gez, the NIH has historically received criticism from the ME/CFS community in terms of their handling of the condition. They've endeavoured to bring on a lot more patient involvement. Tell me your thoughts on their proposed ideas.

Gez Medinger (14:40): The principle of putting together a strategic roadmap for a condition like this that has eluded academic consensus over the last 30 years — you could spend a century going down blind alleys. Any research project has a five-year time horizon. So spending time, even years, to understand the highest probability avenues and order them by priority, then choosing which to run concurrently, is of absolutely critical importance. Had we had a strategic roadmap 30 years ago, I think we'd be in a very different place now.

Emily Kate Stephens (16:03): One of Dr. Whittemore's key priorities is to create cohesion in the way we gather data. We need people to stop working in completely siloed systems and start looking at the patient as a whole individual. Here is Amy Rochlin, CEO of the Complex Disorders Alliance, who is working to bring together multiple organizations to move the science from labs into clinics and to patients.

Emily Kate Stephens (17:47): One of the exciting things about what you're looking at is you are looking at Long Covid, but also ME/CFS — ME/CFS is being brought into the fray, sometimes as a control, sometimes as a separate marker. I love how your organization has the ability to take people from different organizations and standpoints, scientists and clinicians, and actually bring them together, working toward actually treating patients rather than just abstract theory.

Amy Rochlin (19:07): That's honestly the best part. We stand on the shoulders of incredible science. There has been incredible scientific work done in ME/CFS specifically, but we need to organize it and pull it into the clinic and understand who can be helped. The patient population has suffered because the age-old siloed system doesn't handle complex, multi-systemic disorders well. Long Covid has helped us understand these conditions through another lens — a viral trigger. And we can look at the ME/CFS population where there could be some sort of persistence driving their dysfunction, and we can learn from other conditions. It's about doing things at scale and faster, but it's really, really treatment focused.

Emily Kate Stephens (21:08): Do you think we have clearly defined subtypes in ME/CFS in the same way that they formed in Long Covid?

Amy Rochlin (21:19): I think we're at the beginning of all of it. Science is about learning and change — you learn, you keep moving forward. For ME/CFS and Long Covid, I think we're just at the beginning of these subtypes. But I think pressing on researchers and clinicians to share their subgroups with us so we can test them in our AI-driven systems to even more deeply subtype patients is the direction we need to go.

Emily Kate Stephens (22:19): Another person incredibly respected in this space is Sonya Chowdhury, CEO of Action for ME, who has been heading up Action for ME for the last 14 years. The work they have enabled collaboration on really seems to be making a difference. Here's what she had to say.

Sonya Chowdhury (22:57): There could be researchers out there who have never been involved in ME that, if we can involve them and say this is an area — bring your expertise and come into this illness field — that would be a win for everybody. As an organization, Action for ME became focused on genetics specifically because of our involvement in the DecodeME study. Our involvement has helped facilitate lived experience engagement, and that became a particular niche for us. Because of DecodeME, we set up the Genetics Centre of Excellence — the idea was to accelerate science from a genetic perspective to build on DecodeME, so all that data didn't go to waste.

Emily Kate Stephens (24:47): The mission for Action for ME is "taking action, delivering impact." Your work with patients enables people to feel you are having that impact. Research priority number two is repurposing existing drugs, and your work with DecodeME genetics and PrecisionLife is directing us to a position where we might be able to get treatments for the correct people soon — not 10 years down the line.

Sonya Chowdhury (25:49): Nothing will bring back the people who've spent the last 30 years suffering, but to have treatments — and there will be treatments plural, there will be no one treatment, because there are subsets of ME — people are likely to need quite personalized care. When I started 14 years ago, I wasn't sure I'd see those treatments come to fruition in my tenure. But that feels possible now, and not in 10 years' time, but in the very near future. We've got to approach this from a number of different angles — we need the genetics, which takes time, and we need those novel techniques as well. You need that diversity of perspective, technique, and technology.

Emily Kate Stephens (27:31): What the referencing of DecodeME and the LOCOME study has actually enabled is huge amounts of data analysis across thousands of ME/CFS patients — it is that sort of scale of study that is beginning to drive momentum. I also had the pleasure of talking to Tahlia Ruschioni, Executive Director of the Bateman Horn Center, who are really trying to drive change not just in the science but amongst the patient community.

Emily Kate Stephens (28:33): If you compare where we are in 2026 with your understanding of this condition when you first experienced it within your family, how far have we moved the needle in terms of our understanding of ME/CFS?

Tahlia Ruschioni (29:00): That is a loaded question. Looking back at the NIH research roadmap and what that created for ME/CFS, Long Covid, and these other neuroimmune conditions — the research is being done and expedited in a way we've never really seen until a pandemic happened. We can look at the political landscape right now and start to worry that constraints are being put back on, and yet I think it's already happening. The momentum has moved. From where I started in 2019, begging for people to just let us in, to now people coming to us saying "I'm seeing this, what do I do" — that change is so positive. I know hopeful is a dangerous word to use, but we are seeing it start to happen.

Emily Kate Stephens (30:53): I've seen a shift in this space in the last six years. About three years ago, there was anger in the ME community that Long Covid had taken up resources in an area people had been begging for decades to have help with. But that spotlight has now begun to swing round to encompass ME/CFS. Once people started seeing that ME/CFS researchers had been brought in and formed an integral part of the NIH roadmap and the RECOVER TLC initiative, I feel like there's a little more cohesion between the two worlds. Long Covid may have enabled us to do something in ME/CFS that the pandemic's scale made possible.

Tahlia Ruschioni (32:37): For Bateman Horn, we saw it as an opportunity to finally get ME out there. We opened an entire Long Covid arm in 2021 knowing that within six months, patients could be meeting the criteria for ME/CFS. It gave us a window to see it when it first started, and then to see how that changes over time. Can earlier interventions help? It's all individualized. I think it's really hard when you're inside this body to see that change is happening, but the pandemic gave us a window to be able to do what ME has long been needing: the lens for everybody to start taking this seriously and put the resource and funding behind it.

Emily Kate Stephens (34:40): Tahlia mentioned individualized interventions — this is where we've been struggling for so long with ME/CFS, the fact that it has been treated as one disease. I was therefore hugely excited by the DecodeME study and by a company called PrecisionLife, who do AI precision medicine for complex disease, working with that DecodeME data. Here is a conversation with their CEO, Steve Gardner.

Emily Kate Stephens (35:49): You said that we are in an early stage of the disease, yet people will say we are 30 years down the line in trying to understand it. How far do you feel we have come as a scientific field in terms of our understanding and what we have the potential to do for ME/CFS patients?

Steve Gardner (36:24): I think we hit a transformational point with the publication of our last paper. It was a collaboration between ourselves, DecodeME, Action for ME, and Innovate UK who funded the LOCOME project. What that paper showed is that it's not that we can't find the genes associated with the disease — it's that there are too many genes associated with the disease. This is not one disease. It's polygenic and heterogeneous. The tools set up to deal with cancer and rare disease just don't work as well when you have that level of complexity. We've now proved that there are hundreds of genes involved. Therefore our understanding of how we should study this disease and design clinical trials is fundamentally different from where it was three or four years ago. We have to do stratification, like we do with cancers. We have 260 genes we can go after, and 42 repurposing candidates we can trial. We've switched the light on, and now we can see all the major points on the map. I think that is a profound shift.

Emily Kate Stephens (39:55): That is incredible. You wrote that the study reinforces that ME is a complex, multi-systemic condition with a clear genetic basis. For patients, that takes it from being something so stigmatized and blamed on the patient to having scientific evidence that there is a genetic basis for it — which is remarkable.

Steve Gardner (40:29): It's unarguable now. While we were trying to find one SNP or one gene, everybody had their own theory — and they were probably all right, but not for the same patient. Now we have unequivocal, peer-reviewed, multiply replicated results that demonstrate there is a really strong biological basis for the disease.

Emily Kate Stephens (41:08): Gez, am I over-excited about this science?

Gez Medinger (41:12): I don't think so. The genetics angle is a brilliant sidestep to the phenotyping problem we've got, because we still don't have a clear idea of what these phenotypes should be. Even once you identify phenotypes one through five, the causes driving very similar symptom presentations may not be the same mechanism. With your genetic makeup, you might need medications one, three, and four, while someone with the same symptoms needs two, four, six, and eight. This is a much more precision targeted approach. What becomes slightly more difficult is: can you imagine going to your GP and getting a genetic test? That feels like it's still some way off. But if we start to get some RCTs showing proper effectiveness, it might actually force some rethinking of service provision for people with ME/CFS.

Emily Kate Stephens (43:09): One thing to say from DecodeME — which is what enabled PrecisionLife to do their data analysis — is that DecodeME gathered that information from a home spit test. They sent out spit kits to 16,500 people. This still actually prevented people with very severe ME from contributing, because even producing that amount of saliva or filling in the questionnaire was too much. However, it did manage to gather data from a huge group often missed from studies requiring travel to a test site. The way this kind of testing filters down into a GP surgery will be challenging, but patient organizations are involved in the design, and we are stepping in the right direction with less invasive testing producing much broader results.

Gez Medinger (44:43): Listening to Steve's interview, it felt like over the last decades we've had different researchers and clinicians standing on different islands in the Pacific Ocean, trying to communicate with each other from their own points of perspective. What it feels like now is that we've got a bit of flat land, built on a solid scientific basis, that we can build out from — a bridge that links some of these islands together. This is a really powerful building block for establishing where we go from here.

Emily Kate Stephens (45:36): This kind of science actually corroborates all of those researchers in being entirely correct in their hypotheses, and hopefully brings together an understanding as to why they were right — and how they are not necessarily right in all cases. The idea of individualized care from this potential testing is huge.

Gez Medinger (46:10): I think it's going to be essential. We've been saying for a long time it's never going to be one magic pill for everybody — it's always going to require personalized, holistic care. But we haven't really known what that might look like. Now I think we're getting a sense for it.

Emily Kate Stephens (46:27): I wanted to bring another voice — someone from a different angle. This is a short comment from David Tuller. He is a senior fellow in public health at the University of California in Berkeley and has been working as an advocate for ME/CFS patients since he challenged the results of the PACE trial. His work enabled momentum to change guidelines that had been given to ME/CFS patients — guidelines that ran for almost 10 years before NICE changed them in 2021.

Emily Kate Stephens (47:54): Do you think there are exciting studies, specifically in ME/CFS, coming out of the UK and Europe?

David Tuller (48:01): I think the DecodeME study, which was a genome-wide association study done out of the University of Edinburgh and funded largely by the UK government, found certain points on the genome suggesting genetic links that had a role in the pathogenesis of the illness. Those were exciting findings. But to develop anything from that takes a long time, between that and actually getting medications to people — which is what people want.

Emily Kate Stephens (48:47): Well, there are still huge leaps to make — we need to identify the genetic components, work out who would actually benefit from what sort of treatment, and then develop the treatments that would help them. Do you think we have travelled some distance since you first started looking at this?

David Tuller (49:20): I think we've travelled some distance in the sense that more people recognise there's a clinical entity there, it's not just a mishmash of people complaining about symptoms. A lot of patients would say they don't experience that difference on the ground, and that depends upon the country. In the US, if you have good insurance and access, you can choose care you prefer. In places with a national health care system, you have less choice. In the UK, I still hear all the time about people whose GP doesn't say or do anything, and they don't really have an out. So what's happening at the research level and what's happening at the level of patient experience are different.

Emily Kate Stephens (50:32): So I think this is the age-old problem, Gez. I wanted to bring hope with this conversation and understanding, but it still comes back to how does it reach the patient. Great ideas — but how do they translate down? Back to Amy Rochlin on the power of actually working together.

Amy Rochlin (51:00): Understanding who the key players are and bringing them together is really exciting for us. I want to highlight the collaboration across organizations who could be seen as competition: nonprofits, Action for ME, SolveME, OMF, Poly Bio, the Schmidt Initiative. Sonya Chowdhury was able to bring together CODA, SolveME, the Schmidt Initiative, and Long Covid Research ME to do early funding of Sequence ME and Long Covid — which is going to build the largest longitudinal long-read database to be analysed for ME and Long Covid. That collaboration yielded 4.5 million pounds of support from the UK government. Not one group is going to solve this whole thing, so we're going to do better together.

Emily Kate Stephens (53:06): I love the collaborative approach. The fact that coming together provoked the UK government to give 4.5 million pounds shows our audience that through organizations such as yours there is real movement — not just small grassroots movement. We are talking about big investment. Approaching it with this business brain enables us to move from small scale individual studies to creating a huge movement together.

Amy Rochlin (53:36): I think you've hit it on the head. The hope is that by us all coming together, you feel the impact of what we're doing. It is a system of making this work faster, but I know it's not fast enough — and I mean that sincerely. I still lie awake every night thinking about the people I've spoken to. I am determined, and I find other determined people so that we can move faster, because people are so sick. I just refuse to accept that that has to be. I think with some additional work, we can make this happen faster.

Steve Gardner (55:14): There's more science to be done, more research and validation work, but these are stepping stones we need to make with the disease in order to understand it better, and to have those tools that we could then use in the clinic once we do have some medicines that work, to guide people towards things that are actually going to be effective for them.

Emily Kate Stephens (55:48): For them — and that is the key to what you're trying to do. Gez, what do you think of the whole picture?

Gez Medinger (56:04): I think one word I would like to pull out from it is hopeful, and I think that is fair, but it's still going to require patience. We may have a very effective roadmap to go forward from. We may have some science that has created bridges between these silos and their islands, and we can actually start to build a rocket on those bridges that can fire off with effective treatments. But that's going to take RCTs, and this isn't like we've discovered a bacterial infection and just need to trial some antibiotics. The treatments we need to trial through phase 1, 2, and 3 are complex, with different combinations. Five years is optimistic.

Emily Kate Stephens (56:56): Although we are not necessarily talking about developing whole new drugs and bringing them to market — there are drugs already in production that could be repurposed — there is still that process of randomized controlled trials needed to understand their efficacy in this condition. As we know from graded exercise, what is appropriate in other conditions is not necessarily safe in ME/CFS. You can't just make that assumption.

Gez Medinger (57:40): Very true. There is a degree of complexity to where we go from here, even if it feels like we've got a really good platform to start jumping off from. It is going to require a huge amount of collaboration and good science, and funds ultimately. So, yes, it is hopeful, but the other key word is patience. In the meantime, we just have to look after ourselves as best we can.

Emily Kate Stephens (58:08): And look after each other. But it definitely gives me hope to know that there are these people who are genuine forces of nature out there trying to make a difference to the population of people with ME/CFS who have effectively been ignored for decades. Gez, it has been an absolute pleasure. I very much look forward to the next time that we get to do this.

Gez Medinger (58:37): Me too.

Emily Kate Stephens (58:40): Thank you for listening to Make Visible. Please do like, follow, or subscribe to listen to our next episode, where we'll be uncovering more insights into complex chronic illness. This was brought to you by the team at Visible, a group of scientists and engineers whose lives have been affected by energy limiting health conditions. We're building wearable technology that's helping 100,000 people measure and manage their complex chronic illness. To find out more, visit makevisible.com.