Researchers are unraveling the mysteries of joint and tissue damage due to RA.
You live with rheumatoid arthritis (RA) every day. But what’s happening inside your body that sets inflammation and joint damage in motion?
One simple way you may explain RA to others is that you have an autoimmune disease. Your body’s immune system goes haywire for some reason. Cells that normally fight agents of disease attack your healthy tissue instead. We don’t really know why this breakdown happens, but exciting new RA research may tell us more.
The Latest RA Research
Leading scientists who study RA want to know what goes wrong in autoimmunity at that very basic level: Your cells. Which type of immune cell plays the most damaging role in RA, and what mechanisms are involved? If we learn more about what’s going on in RA autoimmunity and joint damage, we may be able to develop more effective, targeted drugs to treat it.
Most current RA medications try to tamp down your inflammation and disease activity by blocking your immune system’s production of particular cytokines, or pro-inflammatory proteins. The ultimate goal of RA research is a cure—a treatment that might fix the errant activity of immune cells, so they behave normally again.
That goal is still a long way off, but we are getting a little closer. At the Stanford University School of Medicine in California, researchers published a study in the journal Nature Immunology that unravels more about RA’s mysterious behavior, and reveals a new, experimental compound that may be able to reverse the damage-causing processes in RA1.
1Wen Z, Jin K, Shen Y, et al. “N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation.” Nature Immunol. 2019 Feb 4;(20):313-325.
The scientists already knew a few important clues about RA from their past research:
- One: RA is a malfunction of your cell metabolism, or the chemical changes inside your cells as they do their work. When you have RA, something goes wrong in your cell metabolism. Immune system cells behave incorrectly and cause unhealthy activity in the form of inflammation and joint damage.
- Two: Everyone has T-helper immune cells, including healthy people. But in people with RA, T-helper cells have low amounts of adenosine triphosphate, or ATP. This molecule stores and processes energy in cells so they function normally. Your T-helper cells should make lots of ATP, but in RA, they don’t. Instead, they make less ATP and more of other, bad-acting molecules that promote inflammation and damage.
- Three: Why are ATP levels low in people with RA? The researchers at Stanford knew one molecule, AMPK, likely plays a role in this breakdown of normal cell behavior. AMPK usually keeps track of how much ATP your T-helper cells make. If AMPK senses that you’re not making enough ATP, it corrects the problem. In RA, AMPK isn’t switched on to do its job. Usually, AMPK connects to lysosomes, which are tiny trash collectors for all of your cells.
Once they connect, together they collect and recycle waste products. They also make sure that your body makes the right amount of ATP for a healthy immune system. In RA, AMPK doesn’t bind to lysosomes for some reason. Your body doesn’t make enough ATP. Your immune system’s healthy function goes haywire and triggers inflammation that attacks your joints.
Why is this happening? The team at Stanford wanted to find out. They collected blood samples from 155 people with RA, as well as blood from healthy people and people with other types of autoimmune disease for comparison. They pulled T-helper cells out of all of the blood samples and examined the cells under a microscope.
What they learned: First, they found out people with RA, people with other autoimmune diseases and healthy people all have the same amount of AMPK, but in RA, the AMPK isn’t switched on. They also found that the AMPK in RA has much lower amounts of myristic acid and an enzyme called NMT1. Both NMT1 and myristic acid help AMPK connect to lysosomes so your immune system can function in a healthy way, but these low amounts in RA are a red flag.
What they were able to change: Could this malfunction be fixed somehow? The researchers at Stanford experimented on specially bred mice in their lab. When they injected these mice with T-helper cells from the RA blood samples, the mice had severe tissue damage. Then, the researchers injected the mice with T-helper cells with pumped-up amounts of NMT1. Those mice had much less inflammation and tissue damage.
New discovery: The most exciting result from these experiments was a new compound that the researchers developed called A7669662. That’s not a very catchy name, but the researchers found that A7669662 was able to switch on AMPK and even reverse the bad behavior of the T-helper cells in mice.
What this means—and what it doesn’t: These exciting discoveries could point the way to the development of new, more effective treatments for RA. Scientists will continue to investigate all of these cells and molecules to see what really goes wrong in RA and how to fix the process. However, this takes many years of research and testing.
Scientists have to repeatedly test any new, experimental substance before it’s even considered a drug candidate. Just because a compound works in mice doesn’t mean it will work the same way in people. Drug development is a long, costly process, but every exciting discovery is another step toward better treatments for RA and, one day, a cure. Also, more powerful drugs may have side effects that we don’t know about yet2. That’s why it’s so important to support RA research. Scientists believe a cure for RA is possible and won’t give up until we get there.
2Scott DL. “Developing new therapeutic approaches for rheumatoid arthritis: the continuing challenges of clinical assessments.” F1000Res. 2016; 5: F1000 Faculty Rev-2019.
Know your Score: Keep track of your levels of RA inflammation. Your Vectra® report now shows your future risk of joint damage (also called radiographic progression, or RP) within one year. This shows you if you’re at risk for worsening joint damage due to RA disease activity, so you and your doctor can make changes to your treatment plan if needed to get back on track. Your Vectra Score is personalized to reflect your age, sex and level of body fat. Tracking your Vectra Scores over time helps you and your doctor know how well your treatment is working. Visit VectraScore.com to learn more.