Fire Inside: The quest to understand & prevent rheumatoid arthritis

In the early '80s, Linda Sloate was a 30-year old mom raising three little kids when she became one of an estimated 20 million people worldwide living with rheumatoid arthritis (RA). It has been a 40-year struggle filled with dozens of treatments and surgeries. Today there is new hope for patients as researchers have come together for a collaborative project to uncover how RA begins – and how to stop it in its tracks.

Behind every science headline, there is a human story. Hear about the scientific advancements aiming to shape the cures of tomorrow with Lab Notes: A podcast from the Allen Institute. Streaming everywhere.

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Linda Sloate 

“Before I had this disease, my life was very, very active. I would water ski, snow ski, jump up and down. crawl on my knees. Work in the yard on my knees. I would climb trees to prone things. I would run after my grandkids or my my kids. I would run after dogs and then I get the disease and all that, all of a sudden stops. You can't crawl like you're used to. You can't jump like you used to You can't walk like you used to. That's what RA does to you.” 

Rachel Tompa 

R.A., rheumatoid arthritis. It’s an autoimmune disease that attacks tissues near joints and other body parts, including the lungs. It can be incredibly painful and debilitating. 

Linda Sloate’s arthritis may not seem that unusual for her age — she’s 70 this year. But unlike many others her age, she’s been living with the pain for more than 40 years now. She was diagnosed with rheumatoid arthritis when she was just 30 and mom of three little kids.  

It’s a relatively rare form of autoimmunity that affects about 20 million people around the world. And while there are treatments that work for some — there is currently no cure. 

Rob Piercy 

Today, we’re sharing the story of Linda’s decades living with rheumatoid arthritis — and a team of researchers who are trying to understand how the disease starts — and how to stop it in its tracks.  

Kevin Deane 

“I’m going to go out on a limb here and say, I would hope that within the next five to 10 years, we'll have a big step forward for prevention. And maybe in 15 to 20 years, it'll be fully integrated into how we handle rheumatoid arthritis. We’re really getting close to understanding how we can prevent disease.” 

Rob Piercy 

I’m Rob Piercy 

Rachel Tompa 

I’m Rachel Tompa. And this is Lab Notes, a podcast from the Allen Institute. 

Linda Sloate 

“You always have to put a smile on everyday. And count your blessings.” 

Rachel Tompa 

It’s mid-morning on a blue-sky Seattle wednesday and Linda Sloate is doing something most of us take for granted: she’s putting on socks and shoes to go for a walk. 

Linda Sloate 

“And right now, I’m counting my blessings because I have new feet. And it would have taken me a lot longer to put these shoes on with my old feet.” 

Rob Piercy 

Linda is less than two months post-op from a surgery to reconstruct her feet. Rheumatoid arthritis had deformed them to the point that normal shoes no longer fit. 

…One obstacle of many in her decades-long battle with R.A. 

Linda Sloate 

“On a bad day with RA, without any medicine, you feel every part of your body hurting from the top of your head, to your teeth, to your neck, to the covers on your when you're sleeping, they're hard to move your fingers hurt your toes. I mean, it's from the top to the bottom of your body.” 

Rachel Tompa 

Forty years ago, Linda Sloate was a young mom raising a family with her husband Mike. 

Linda Sloate 

“I did a lot of sewing, I always made their clothes, you know, my boys not so much they didn't when they were babies, yes. But when they got older, they didn't want, you know, these shirts and everything that I've learned, you know, in shorts, that I would make them. But I did a lot of sewing for my daughter.” 

Rachel Tompa 

In time, all of the fabric snipping and sewing became increasingly painful. 

Linda Sloate 

“And I thought my hands were really starting to hurt. And I thought, well, you know, at nighttime, I couldn't go to bed without getting cramps in my shoulder. I thought, jeez, you know what's wrong, you know, so my girlfriend's husband was a tin snipper at bethlem steel, or not Boeing, and he had carpal tunnel. And she explained to me what that was. And I said, Ooh, that's almost like the way I feel. So I went to a doctor, sure enough, they found out I had carpal tunnel in both of my hands. And so they did the surgery on my hand and back then, would have been in the 80s. They didn't biopsy any of your, you know, the things that they took out of you. So at that point, you know, it was just carpal tunnel.” 

“And then after I had the surgery, my feet started really bothering me. And I started getting symptoms of having the flu. And when you're trying to raise three kids, it was really hard to be, you know, sick, you know.  

Rachel Tompa 

Maybe not everyone knows this, but rheumatoid arthritis can affect more than just the joints — it can cause overall body aches and flu-like symptoms. 

Linda Sloate

“So, I thought, oh, this, you know, something's not working right here, you know. I thought I, you know, I better check this out. So, I went to the doctor, and I went to my normal doctor, and he said, ‘Well, I'll take some blood work and, and he said, You know, I think you might have some type of arthritis, he said, but we need to do another blood draw to see if you do have it.’” 

Rob Piercy 

A few days later — the phone rang. 

Linda Sloate 

“And he called me and said, ‘The signs are rheumatoid arthritis.’ I thought rheumatoid arthritis, was for old people. And I was not old, you know, I was 30. I never thought that somebody young, could get this disease.” 

Rob Piercy 

The news was devastating.  

Linda Sloate 

“Now there are a lot of support groups. Back then, you know, there weren't any support groups that you could say, this is how I feel, you know, and I just knew I had to keep going, you know, because I had to raise my family.” 

Rachel Tompa 

It was the early ‘80s. There were treatments for rheumatoid arthritis, but none of them was very effective for Linda. For decades, one of the mainstays of rheumatoid arthritis treatment was injections with gold salts — but it didn’t work very well for many people. 

Linda Sloate 

“Right away, you know, put me on gold, methotrexate, and all these drugs that were out there at the time, which then they made me really sick. Also, you know, so I thought, Oh, this is, you know, not the best way to live with three kids, you know.” 

“When I had the gold shots, you know, like the fifth shot and they have to do it in your bottom. It was very painful and then nothing would happen. You know, the pills made you sick. I lost weight with methotrexate and so then he was doing gold shots, methotrexate, then just methotrexate then prednisone. I had just numerous different ones that never worked and made me ill. Nauseousness hair loss. Worst achy body ever. flu symptoms, joints aching worse than they normally do. Hard to get up in the morning was you know, it was hard. It was very frustrating.” 

Rob Piercy 

Despite all the pain and the frustration — Linda is, by nature, an eternal optimist. 

Her husband Mike: 

Mike Sloate 

“So, it's just Linda. Her attitude is so great. And if you talk to any one of her girlfriends, they will say that, she has that spirit and that drive, nothing gets her down. Nothing."

Linda Sloate

“I think the biggest thing is when you find out that you get a disease, you have to have a positive attitude. Because you're here to live your life. And if you live it miserably. It's not healthy for you.” 

Rachel Tompa 

So, Linda went to work at a nearby catholic school. With swollen hands, she’d tie dozens of shoelaces every day. 

Linda Sloate 

“When the kids that I worked with saw my hands, they thought, you know, ‘Why are your hands so large? You know, they're not supposed to look like that,’ you know, and one of the kids in my class, you know, when they're kindergartener, they say anything. And he said, ‘Hey, Mrs. Sloate, why are your hands so big?’ And I said, ‘Well, I have rheumatoid arthritis.’ And I explained to him what it was. And he said, ‘Well it’s a disease can you give it to me?’ I said, ‘No, I can't give you this disease.’ And he says, ‘Well, if you ever ran into a burglar, you could always give him a good wallop!’” 

Rachel Tompa 

For people with rheumatoid arthritis, the inflammation in their joints can be so severe that it causes permanent disfigurement. Linda’s hands and feet were getting to that point already.  

Linda Sloate 

“Any picture that I would take my hands would never be in the front, they'd always be behind me. I would try to get in that angle of the picture where they wouldn't see my feet. You know, that's, that was hard, you know? And you'd have to use your hands all the time. You know, like writing something and people would look you know, and they'd say, Oh, you know, what's wrong with your hands? They wouldn't say it but they you could tell that they were looking and wondering.” 

Rachel Tompa 

And Linda was wondering when her doctors would figure out a treatment that worked. 

Linda Sloate 

“But you know, I just figured, well, they know what they're doing and not getting any better. But maybe something's gonna happen. You know, I kept waiting for that to happen. But it wasn't. So, I think that's when my doctor, he was really into a lot of research and he was trying to get a program together with this new drug that was coming out. And I think that's how I started in the Enbrel study.” 

Rob Piercy 

Enbrel is the brand name of the drug etanercept, which came out in the late ‘90s. It’s what’s known as a “biologic”. Biologic drugs are produced from living organisms, or contain parts of living organisms. In the case of Enbrel, it’s synthesized inside hamster ovary cells in petri dishes in the lab. Given by injection, it works by tamping down a protein that’s part of our body’s inflammatory immune response. In patients with rheumatoid arthritis, that immune response — for reasons not fully understood — goes out of control.

The day after Linda got her first Enbrel shot? 

Linda Sloate 

“I could not believe the way I felt, I was like, Oh, my gosh, this is a miracle in the mornings before, I would have to pull my fingers apart, because there were like little balls, and barely walk from my feet, you know, just to get up. And I was able to get up, my hands weren't, you know, together in a ball. And I was able to go outside on a cement floor without any shoes on. And I thought this is a miracle. And ever since it's been like that. So, you know, it was a miracle. It really was.” 

Linda Sloate 

“This is my Tuesday morning of giving myself my Enbrel shot. Which I mix-up. They come in all these little safety things that you have to get off… sort of hard sometimes.  Especially when you have hands that are hard to make these things work.”

Rachel Tompa 

Linda’s been on Enbrel now for more than 20 years. It’s helped her lead a more normal life.  

But for other patients — Enbrel and other drugs like it — isn’t the wonder drug that it has been for her. 

Kevin Deane 

“I think that speaks to the concept that rheumatoid arthritis while we call it one disease has several subtypes. And so certain people may not respond to all therapies.” 

Rob Piercy 

That’s Dr. Kevin Deane, an R.A. researcher and clinician from the University of Colorado Anschutz Medical Campus. Deane and his colleague Dr. Michael Holers, who heads the Division of Rheumatology at CU Anschutz, have been working to understand how rheumatoid arthritis begins. 

“A dominate hypothesis that we've played a major role in developing in Colorado, is that the disease that ultimately appears to physicians as rheumatoid arthritis is a process that actually starts in various mucosal sites.  

Rachel Tompa 

That means that even though we think of rheumatoid arthritis as a joint disease, Drs. Dean and Holers believe it could actually begin on the mucosal tissue — these are the kind of slimy surfaces of our lungs, our mouth, our digestive tracts. They’re much more sensitive to the environment and prone to inflammation.  

Michael Holers 

The idea is that you normally want to get rid of that inflammation, whatever's causing the inflammation, but for any number of reasons, individuals can't get rid of that inflammation and the immune response which is normally supposed to get rid of it evolves over time to start to target your own body, your own joints, your own tissues.” 

Rachel Tompa 

In the beginning, Dr. Deane says rheumatoid arthritis is like a small candle flame. 

Kevin Deane 

“And then it progresses over time like to a campfire size and then finally a full on forest fire. Unfortunately, when mostly we diagnose people with rheumatoid arthritis there at the forest fire stage, when we can target certain parts of that and dampen those flames, but it's gotten to such a high level that it's really hard to put it out completely. We'll fire get so big, it creates its own weather pattern in lightning and then it can start more fires. Rheumatoid arthritis is kind of like that. The inflammation goes out of control and something new happens that also further dysregulates it. And so, understanding those ancillary processes I think are very important.” 

Rob Piercy 

Together with rheumatologist Dr. Gary Firestein and his lab at UC San Diego School of Medicine, the researchers have partnered with the Allen Institute for Immunology to understand how rheumatoid arthritis begins and how to stop it. 

Michael Holers 

“To use Kevin's forest fire analogy, when the forest is burned down, you don't know how it started. So, there's no retrospective way to figure this out. So, you need to look and see where it starts and how it starts. And that's a hugely important question.” 

Rachel Tompa 

Over the course of three to five years, the team will study 60 volunteers who all have blood markers for rheumatoid arthritis, but who have not yet developed the disease. 

Kevin Deane 

“And then following those individuals over time to watch their progression to arthritis. Throughout that we're studying their blood in depth multiple times a year studying mucosal surfaces, including the lung in the gut to see how that's interacting with their body's total immune system. Once they do develop the classic rheumatoid arthritis, the joint disease, then we get a biopsy of their joint as well. So now we can look at an individual from this early triggering through blood base changes and ultimately a joint disease.” 

Rob Piercy 

The Allen Institute for Immunology has built out a sophisticated research pipeline to process the volunteer bio-samples to get a really detailed look at what’s happening with their immune system over time. 

Kevin Deane 

“So, we will look at each one of those components and say: what are the immune changes here, here and ultimately a joint disease, understand that compared to people who don't get rheumatoid arthritis that are also being studied in the Allen Institute projects. So, we understand these are the abnormal pathways, these are key to developing rheumatoid arthritis, and then being able to build on that identify ways to alter those pathways so people do not progress to disease.” 

Rachel Tompa 

Remember the old saying an ounce of prevention is worth a pound of cure?  

That’s really the hope here… that you could treat people who have markers of rheumatoid arthritis before they ever get the disease — and ultimately prevent it from taking hold. It could be that existing treatments would go a lot farther if people took them before they ever developed symptoms. The research teams are also looking for new drug targets as they sift through the data from the study volunteers. 

Rob Piercy 

It’s not unlike the approach cardiology has taken with people who have a family history of or risk factors for heart disease. Doctors prescribe lifestyle changes, dietary-changes and medications like statins — which lower cholesterol — before heart disease has taken hold. 

Michael Holers  

“So, similarly, what we'd like to do is to be able to identify new therapeutic targets that are in this at risk, asymptomatic phase of rheumatoid arthritis, and use those kinds of drugs in individuals and keep them from developing the disease. Our goal in Colorado working with the Allen Institute and our colleagues at UCSD is to be completely cured completely stopped completely prevented” 

Kevin Deane 

“I’m going to go out on a limb here and say, I would hope that within the next five to 10 years, we'll have a big step forward for prevention. And maybe in 15 to 20 years, it'll be fully integrated into how we handle rheumatoid arthritis. We’re really getting close to understanding how we can prevent disease.” 

Rachel Tompa 

For Linda Sloate… it’s progress with promise for the future. While rheumatoid arthritis has not yet been proven to be hereditary, it does appear to run in some families and researchers believe there is a genetic component. Linda has always feared her children and grandchildren may have to live through what she did. 

Linda Sloate 

“My grandkids, there's hope, you know, for the future of the kids that are out there that have these diseases, or their parents have them or their grandparents have had them, you know, there's hope that there'll be treatment for these children that might have something. Almost makes me cry, because I don't want them to have these hands. Or the feet, or the achy body, I don't want that. So, I don't want anybody to have that. 

My hope is that one day, this is going to help everybody. You know, it's just going to be a miracle. And I know it will be because it's just gonna happen. I know it.” 

Rob Piercy 

During our interview, Drs. Deane and Holers emphasized their gratitude to the volunteers participating this study. Their generosity of time and of themselves is invaluable. The research simply wouldn’t happen without them. 

Linda Sloate is a volunteer in a different study at Benaroya Research Institute at Virginia Mason — which has also a partnered with the Allen Institute for Immunology for studies of immune health. 

Rob Piercy 

I’m Rob Piercy 

Rachel Tompa 

I’m Rachel Tompa. For more lab notes episodes and science research news, visit our website — alleninstitute.org

Rob Piercy 

Thanks for listening.