Today, more than 350 million people across the world – and nearly a quarter of American adults – have arthritis. A condition characterized by pain, inflammation and stiffness in the joints – often owing to a hyperactive immune system causing the body to attack its own joint tissues, in the case of rheumatoid arthritis – it is a degenerative disease that has no cures to date despite ongoing research.
While current approaches involve physiotherapy, anti-inflammatory drugs to delay disease progression, and surgery to limit the impact of the disease, stem cell studies and biologics have shown therapeutic promise. Moreover, recent findings of links between arthritis and other diseases encourage uncovering drug targets to combat arthritis. As we observe Arthritis Awareness Month in May, here are five recent advancements in arthritis research over the past year.
Acelyrin’s drug candidate advances in phase 2 clinical trials for psoriatic arthritis treatment
For the treatment of psoriatic arthritis, a type of arthritis that affects those with the skin condition psoriasis, the drug candidate izokibep, obtained positive results from a phase 2 trial conducted by U.S.-based biopharma Acelyrin.
The study was a randomized double-blind, placebo-controlled clinical trial that investigated the candidate’s efficacy for three dosage groups – 80 mg izokibep, 40 mg izokibep and 40 mg izokibep placebo. Izokibep is a small protein therapeutic that aims to inhibit interleukin-17A (IL-17A).
Results indicated an ACR50 response – an arthritis treatment measurement that means there is a 50% improvement in tender and swollen joints – of 79% of patients in the 80 mg izokibep group and 50% in the 40 mg izokibep group, at the end of 46 weeks. A psoriasis area and severity index (PASI) 100 (PASI100) score for 50% of participants in the 80 mg izokibep group was observed, although for the 40 mg group, this was 33% at 46 weeks.
“Building on the 16-week data for izokibep reported at EULAR (The European Alliance of Associations for Rheumatology) and ACR (American College of Rheumatology) last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis and enthesitis,” said Philip J. Mease, director of Rheumatology Research at the Swedish Medical Center in Seattle and investigator in the izokibep PsA program.
In 2022, Acelyrin obtained $300 million in a series C funding round to advance phase 3 trials for izokibep.
Interneuron crosstalk could lead to rheumatoid arthritis, research finds
A chronic autoimmune condition, rheumatoid arthritis is typically treated with disease-modifying anti-rheumatic drugs (DMARDs) and biologics, an up-and-coming class of drugs. But a recent study suggests the possibility of a new drug target, broadening current therapeutic measures.
The research led by Hokkaido University in Japan, discovered that adenosine triphosphate (ATP) is secreted in the joints, which could aggravate or even cause inflammation. The scientists tested the hypothesis that neural crosstalk could be responsible for remote inflammation on mice, where the sensory neural circuits between the left and right ankle joints were interrupted. This revealed that a sensory neuron connection through the spinal cord, which transmits the inflammation signal from one joint to the other, is to blame. An increase in ATP in both joints was found to have triggered inflammation.
Therefore, blocking the channel could curb inflammation, making the pathway a therapeutic target to be reckoned with.
Could regenerative medicine cure arthritis?
Growing research in regenerative medicine has proven its scope time and time again, with its potential being realized in treating conditions like leukemia and neurodegenerative diseases. Over the years, studies have demonstrated the possibility of stem cell therapy curing arthritis.
In a study published in 2023, which looked into whether autologous mesenchymal stem cells (MSCs) injections improved the symptoms of knee osteoarthritis in patients undergoing intra-articular injection of bone marrow aspirate concentrate (BMAC) injections as well as those undergoing injections of adipose-derived stromal cells (ADSCs), it was found that according to the measures used to determine the severity of osteoarthritis – like the knee injury and osteoarthritis outcome score (KOOS), Oxford knee score (OKS), and visual analog scale (VAS) – both treatment groups showed significant improvement at the six-month follow up.
Mesenchymal stem cells (MSCs) are stem cells that can develop into more than one cell type, making them key to regenerative treatment for osteoarthritis. Lushun Wang, senior consultant orthopaedic surgeon and medical director of Arete Orthopaedic Clinic in Singapore, said: “While continued research and innovation are still required in this field, current headways can lead to the development of even more effective treatments in the future. For example, mesenchymal stem cell therapy for osteoarthritis cannot be clinically applied yet, but its promising results are steps towards alternatives or even cures to osteoarthritis.”
“Even if we are currently unable to induce cell regeneration and cartilage repair today, advancements like these show that it could one day be possible, or at least slow relating issues and flaring symptoms. Other advancements and similar research are leaps and bounds forward for those living with arthritis – they could mean a world of difference – providing hope and making daily tasks easier.”
Based on another study that compared total knee replacement and intra-osseous BMAC stem cell therapy, where patients were given different treatment on each knee, it was observed that with intra-osseous BMAC – meaning that the injection was administered to the bone – there were similar improvements in pain and function, according to Dr. Zachary Fisk, founder at Acute Pain Therapies in the U.S.. As a result, it became clear that BMAC can be an alternative to total knee replacement.
Fisk said: “Regenerative medicine remains a promising field for management of osteoarthritis. The rate of publication for regenerative medicine interventions continues to grow at an exponential rate. Within the last year or two, there have been some landmark studies that support use of regenerative treatments and encourage further research, given promising early results. Regenerative medicine remains early in its development as a specialty. Studying regenerative interventions in knee osteoarthritis remains the most predominant form of research as knee arthritis is the number one cause of limb debilitation in arthritis patients.”
Research reveals that maintaining dental hygiene could lower risk of arthritis
While brushing our teeth twice a day is a ritual dentists insist we live by to ensure oral hygiene, a study has found that it could even potentially prevent rheumatoid arthritis flares. The research led by computational biologist Vicky Yao at Rice University in the U.S, revealed that there might be a link between periodontitis and rheumatoid arthritis.
Periodontitis is a gum infection that causes damage to the soft tissue around the teeth. The bacteria associated with periodontal disease was found in samples that were collected from people with arthritis, when Yao was working on another project that was investigating the changes in gene expression during rheumatoid arthritis flare-ups.
“One of the things that came up when we were discussing this was, how cool would it be if you could prescribe some kind of mouthwash to help prevent rheumatoid arthritis flares,” said Yao, who hopes to find oral microbial links to cancer, to be able to come up with wider diagnostic measures.
“And if experiments confirm a causal link between a specific virus or bacteria and a type of cancer, then, of course, that could be useful for therapeutics,” she said in a statement.
As mining the gut microbiome has helped understand other conditions like Parkinson’s better, studying the oral microflora further, could be crucial in effectively treating gum diseases as well as rheumatoid arthritis.
New drug could stop osteoarthritis from getting out of hand
Previously studied in the treatment of acne, psoriasis and other skin disorders, research into Talarozole was discontinued. But a recent study by the University of Oxford in the U.K. has rekindled research, but this time around, investigating its potential to treat hand osteoarthritis.
Hand osteoarthritis, which affects the joints of the fingers, occurs when excess synovial fluid – which, in normal amounts, lubricates the joints – and a decline in protective cartilage, which cushions the joints, lead to joint swelling. The disease mainly affects women, particularly around the time of menopause.
According to the study, Talarozole, which inhibits the metabolism of retinoic acid, was found to have suppressed inflammatory genes in mouse models. A decrease in retinoic acid has been associated with being at risk for developing the disease, with the molecule playing a predominant anti-inflammatory role.
“This research is still at an early stage, but with these encouraging findings, we are a big step closer in being able to develop a new class of disease-modifying drugs to treat osteoarthritis, prevent chronic pain, and enable people to live well with the condition,” said Neha Issar-Brown, director of research and health intelligence at Versus Arthritis, a U.K.-based charity that funded the research.
New technologies related to arthritis
- Novel Treatment for Rheumatoid Arthritis – Queen’s University
- Human Cytolitic Fusion Proteins – University of Cape Town
- Rheumatoid Arthritis Biomarkers to Predict Sustained Remission and Flare – University of Glasgow