Currently, more than 350 million people worldwide – and nearly a quarter of American adults – have arthritis. A condition characterized by pain, swelling and stiffness in the joints – often due to a hyperactive immune system that causes the body to attack its own joint tissue, in the case of rheumatoid arthritis – this is a degenerative disease that has no cure to date despite continued research.
While current approaches involve physiotherapy, anti-inflammatory drugs to delay disease progression, and surgery to limit the effects of the disease, stem cell studies and biologics have shown therapeutic promise. In addition, recent findings about the relationship between arthritis and other diseases prompted the disclosure of drug targets to combat arthritis. As we observe Arthritis Awareness Month in May, here are five of the most recent advances in arthritis research over the past year.
The drug candidate Acelyrin is advancing in a phase 2 clinical trial for the treatment of psoriatic arthritis
For the treatment of psoriatic arthritis, a type of arthritis that affects those with the skin condition psoriasis, the drug candidate isizokibep, obtained positive results in a phase 2 trial conducted by US-based Acelyrin biopharma.
This study was a randomized, double-blind, placebo-controlled clinical trial investigating the efficacy of candidates for three dosing groups – izokibep 80 mg, izokibep 40 mg, and izokibep 40 mg placebo. Izokibep is a small protein therapy that aims to inhibit interleukin-17A (IL-17A).
Results demonstrated ACR50 response – a treatment measure of arthritis meaning there is a 50% increase in joint pain and swelling – in 79% of patients in the 80 mg izokibep group and 50% in the 40 mg izokibep group, at the end of 46 weeks. Psoriasis area and severity index (PASI) score of 100 (PASI100) 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 weeks of data for isokibep reported at EULAR (Alliance of European Associations for Rheumatology) and ACR (American College of Rheumatology) last year, the 46 weeks of data now show not only continued but marked improvement over time in the key area 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 a researcher in the PsA izokibep program.
In 2022, Acelyrin secures $300 million in a Series C funding round to advance phase 3 trials for isokibep.
Interneuron crosstalk can lead to rheumatoid arthritis, research has found
A chronic autoimmune condition, rheumatoid arthritis is usually treated with disease-modifying anti-rheumatic drugs (DMARDs) and biologics, an emerging class of drugs. But a recent study points to possible new drug targets, extending current therapeutic actions.
That research led by Hokkaido University in Japan, found that adenosine triphosphate (ATP) is secreted in the joints, which can exacerbate or even cause inflammation. The scientists tested the hypothesis that neural crosstalk could be responsible for remote inflammation in mice, in which the sensory neural circuits between the left and right ankle joints are interrupted. This revealed that sensory neuron connections via the spinal cord, which transmit inflammation signals from one joint to another, were to blame. Increased ATP in both joints was found to trigger inflammation.
Therefore, blocking the ducts can curb inflammation, making the pathway a therapeutic target to be reckoned with.
Can regenerative medicine cure arthritis?
The growing research in regenerative medicine has proven its scope time and time again, with its potential being realized in treating conditions such as leukemia and neurodegenerative diseases. Over the years, research has shown the possibility of stem cell therapy in curing arthritis.
In a Study published in 2023, which investigated whether autologous mesenchymal stem cell (MSC) injections improved symptoms of knee osteoarthritis in patients who underwent intra-articular injection of bone marrow aspirate concentrate (BMAC) as well as those who underwent injection of adipose-derived stromal cells (ADSCs), found that according to measures used to determine the severity of osteoarthritis – such as knee injury and osteoarthritis outcome score (KOOS), Oxford knee score (OKS), and visual analogue scale (VAS) – both treatment groups showed significant improvement at 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 medicine for osteoarthritis. Lushun Wang, senior consultant orthopedic surgeon and medical director of Arete Orthopedic Clinic in Singapore, said: “While further research and innovation is still needed in this area, current advances may lead to the development of more effective treatments in the future. For example, mesenchymal stem cell therapy for osteoarthritis is not yet clinically applicable, but its promising results are a step toward alternatives or even cures for osteoarthritis.”
“Even if we cannot currently induce cell regeneration and cartilage repair today, advances like these suggest that it may one day be possible, or at least slow down the associated problems and widespread symptoms. Other advances and similar research are leaps and bounds for those living with arthritis — it can mean a world of difference — providing hope and making everyday tasks easier.
Based on another study comparing total knee replacement and intra-osseous BMAC stem cell therapy, in which patients were given a different treatment for each knee, it was observed that with intra-osseous BMAC – meaning the injection is given into the bone – there was a similar improvement in pain and function, according to Dr. Zachary Fisk, founder of Acute Pain Therapy in the US. Consequently, it became clear that BMAC could be an alternative to total knee replacement.
Fisk said: “Regenerative medicine remains a promising field for the management of osteoarthritis. Publication rates for regenerative medicine interventions continue to grow at an exponential rate. In the last year or two, there have been several important studies supporting the use of regenerative treatments and encouraging further research, given the promising initial results. Regenerative medicine remains early in its development as a specialty. Studying regenerative interventions in knee osteoarthritis remains the predominant form of research because knee arthritis is the number one cause of limb weakness in arthritis patients.”
Research reveals that maintaining dental hygiene can reduce the risk of arthritis
While brushing your teeth twice a day is a ritual enforced by dentists to ensure oral hygiene, a Study have found that it has the potential to even prevent rheumatoid arthritis flares. Research led by computational biologist Vicky Yao at Rice University in the US, reveals that there may be a link between periodontitis and rheumatoid arthritis.
Periodontitis is a gum infection that causes damage to the soft tissue around the teeth. Bacteria associated with periodontal disease were found in samples collected from arthritis sufferers, while Yao was working on another project that was investigating changes in gene expression during rheumatoid arthritis flare-ups.
“One of the things that came out while we were discussing this was, how cool would it be if you could prescribe some kind of mouthwash to help prevent a recurrence of rheumatoid arthritis,” said Yao, who hopes to find a link between oral microbes and cancer, to be able to come up with diagnostic steps that would wider.
“And if the experiment confirms a causal link between a particular virus or bacteria and a type of cancer, then of course it could be useful for therapy,” he said in a statement.
As gut microbiome mining has helped to better understand other conditions such as Parkinson’s, studying more about the oral microflora could be critical in effectively treating gum disease as well as rheumatoid arthritis.
New drugs could stop osteoarthritis from kicking in hand
Previously studied in the treatment of acne, psoriasis and other skin disorders, research on talarozole is discontinued. But recent research by the University of Oxford in England has revived research, but this time, investigated its potential to treat hand osteoarthritis.
Osteoarthritis of the hand, which affects the joints of the fingers, occurs when an excess of synovial fluid – which normally lubricates the joints – and a decrease in protective cartilage, which protects the joints, causes joint swelling. This disease mainly affects women, especially around menopause.
According to Study, Talarozole, which inhibits retinoic acid metabolism, was found to suppress inflammatory genes in a mouse model. Decreased retinoic acid has been linked to the risk of developing the disease, with the molecule playing a predominant anti-inflammatory role.
“This research is still in its early stages, but with these encouraging findings, we are one step closer to 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 health research and intelligence at Versus Arthritis, a UK-based charity that funded the research.
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