Body clocks, bacteria & a joint-on-a-chip: 2023's best arthritis stories
‘Arthritis’ means inflammation or swelling of one or more joints, but more than 100 conditions affect the joints, the tissues around the joint, and other connective tissue. While symptoms vary depending on the type of arthritis, they commonly include debilitating joint pain and stiffness. In 2023, researchers were focused on better understanding the disease process, and the treatment and relief of arthritis symptoms. Here are the year’s top arthritis stories that appeared on New Atlas.
Mechanism underlying joint inflammation unlocked
Millions worldwide suffer from rheumatoid arthritis (RA). In this incurable autoimmune disease, the body mistakenly attacks healthy cells, causing painful inflammation and tissue damage, commonly in the joints of the hands, wrists, and knees.
Doing a deep dive to determine the disease’s pathophysiology, researchers discovered the pathways by which immunoglobulin G (IgG), our most abundant antibody, influences inflammation. They knew that administering intravenous IgG from healthy donors had an anti-inflammatory effect, so they gave it to mice with RA. They identified the molecular mechanism by which intravenous IgG exerts its anti-inflammatory effect to prevent the joint bone degeneration seen in people with RA. It’s an important discovery that could lead to new treatments for RA and other autoimmune and inflammatory diseases.
Joint-on-a-chip has the potential to transform treatment
Organs-on-a-chip – miniaturized organs that mimic human physiology – took significant strides in 2023. However, one in particular provided some much-needed good news to people with arthritic joint diseases such as RA and osteoarthritis (OA).
Researchers created a tiny 3D organ-on-a-chip that resembles the human joint, complete with blood vessels and synovium. The synovial membrane lines the joint cavity, producing a viscous lubricating fluid that prevents wear. In arthritis, the membrane becomes inflamed (synovitis), causing joint pain and swelling. Being very close to the real thing, this joint-on-a-chip could help researchers understand the disease process better and identify and test new therapies.
Predictability is key to reducing bone and joint deterioration
Aside from medication, exercise is known to be one of the best ways to reduce arthritis pain. But a study found that the interplay between exercise and our circadian rhythm – the biological clock that takes its cues from environmental factors, such as light, dark, and hunger – plays an important role in maintaining bone and joint health.
The findings were clear: our internal clocks like predictability. After the researchers identified a unique clock mechanism underlying skeletal aging, they found that undertaking physical activity at the same time each day allows our skeletal clocks and our central body clock to align, which best benefits our bones and joints.
Bacteria delivers anti-inflammatory without the prick
Biologic disease-modifying antirheumatic drugs (DMARDs) slow or stop the progress of RA by blocking inflammation. They’re administered by injection, either under the skin or intravenously. What if there was another way to deliver an effective anti-inflammatory other than a painful injection?
There soon could be, and it comes from an unlikely source. Researchers genetically engineered a strain of Lactobacillus reuteri bacteria, a probiotic found in humans, to produce a peptide called ShK-235. ShK-235 is an analog of a peptide extracted from the Caribbean sea anemone with known anti-inflammatory properties. In experiments on rats, the researchers found that the probiotic produced consistent and therapeutic levels of ShK-235, reducing signs of disease and paving the way for a daily capsule to relieve arthritic inflammation.
Just because it’s a newer drug doesn’t mean it’s less effective
Janus kinase (JAK) inhibitors are a relatively new addition to RA treatment and work by interrupting the signals that cause inflammation, calming the immune system and relieving the pain of arthritis. Because these drugs are relatively new, few studies have investigated their real-world potential. So, researchers decided to rectify that.
Collecting patient data relating to pain, they compared four JAK inhibitors and found that, for all four, around 90% of patients were still taking the drug six months after starting it. Overall, about one-third saw their arthritis enter remission within that time. Now that the drugs have been proven safe and effective, they might move from being ‘Plan B’ to being a first-line treatment for RA.
From RA to OA: A drug repurposed
OA causes thinning of the joint cartilage and joint surfaces to become rougher, so they don’t move as smoothly. When the resulting pain and stiffness of OA are localized to the hand, it can make it difficult to grasp and hold objects, dress, and eat. About half of people with symptomatic hand OA have synovitis as well (see the above article about the joint-on-a-chip).
One of the first-line treatments for RA is the immunosuppressant drug methotrexate. It’s been around since the ’80s and is cheap and widely available. So, researchers tested it to see how effective it is at treating RA’s close relation, OA. Taking 20 mg of methotrexate once a week for six months produced a reduction in pain reported by people with OA complicated by synovitis, compared to a placebo. The effect commenced at the three-month mark and continued until the end of the trial.
A vaccine that does the opposite of what you’d expect it to do
Ordinarily, a vaccine teaches the body’s immune system to recognize a viral or bacterial invader that needs to be destroyed. Not so the “inverse vaccine”, which does the opposite and could be used to reverse autoimmune diseases like RA.
T cells recognize specific foreign agents on the surfaces of cells and launch an attack. But in autoimmune diseases, the T cells get it wrong and attack healthy organs and tissues, thinking they’re foreign. The liver has a natural mechanism where it sticks a ‘do not attack’ flag on molecules to prevent autoimmune reactions, and that’s what the researchers capitalized on to create their novel vaccine.
Tagging molecules with a sugar called pGal mimicked the liver’s process and prevented the immune system from attacking the body’s healthy tissue in mice with multiple sclerosis, another autoimmune disease. Rather than treating the whole body with immunosuppressant drugs, which is what currently occurs, an inverse vaccine would be much more specific and produce fewer side effects.