New nanoparticles found to be effective for the treatment of rheumatoid arthritis

Figure 1

Schematic illustration of comprehensive and combination RA therapy by Ce-MSCNV nanoparticles. Ce-MSCNVs scavenge the over-produced ROS in an RA knee joint, induce M1 to M2 macrophage polarization for immediate relief of inflammation and symptoms, modulate DCs into tDCs, and finally induce Tregs. CREDIT Institute for Basic Science

A team of scientists led by KOO Sagang from the Seoul National University and Center for Nanoparticle Research within the Institue for Basic Science Center (IBS), in collaboration with researchers from Korea Institute of Science and Technology (KIST) and the Seoul National University, developed a new solution for the treatment of rheumatoid arthritis (RA).

RA is a chronic disease that, unfortunately, has no cure. The disease triggers a mix of troublesome symptoms like inflamed joints, harmful cytokines, and immune system imbalances, which work together to create a relentless cycle of worsening symptoms. While targeting some of these factors can provide short-term relief, others remain unresolved, leading to a frustrating cycle of remission and flare-ups.

One of the major hurdles in RA treatment is the inability to restore the immune system to its healthy state. This leaves the body unable to control the continuous production of harmful substances like reactive oxygen species (ROS) and inflammatory cytokines, leading to persistent inflammation and discomfort.

In essence, the ideal treatment for RA should not only provide immediate relief from inflammation and symptoms but also address the root cause by restoring the immune system to its normal, balanced state.

New nanoparticle-based system as a solution

The new platform involves immobilizing ceria nanoparticles (Ce NPs) onto mesenchymal stem cell-derived nanovesicles (MSCNVs). Both of these components can hinder different pathogenic factors, allowing them to work both individually and cooperatively to achieve a comprehensive treatment.

Ce NPs – can scavenge the overproduced ROS in RA-inflicted knee joints. They also induce polarization of M1 macrophages into M2, achieving immediate relief of inflammation and symptoms.

MSCNVs – deliver immunomodulatory cytokines, which turn dendritic cells (DC) into tolerogenic dendritic cells (tDCs). This consequently generates regulatory T cells for long-term immune tolerance.

In short, this approach aims to bridge both innate and adaptive immunity to achieve both short-term pain relief, as well as convert the tissue environment into an immune-tolerant state to prevent the recurrence of symptoms.

Researchers confirmed the efficacy of this approach using a collagen-induced arthritis mouse model. The Ce-MSCNV system was able to comprehensively treat and prevent RA by simultaneously relieving the immediate and restoring T cell immunity. Supporting data suggest that improvement in conditions can be achieved after only a single-dose treatment.

The mice treated with the Ce-MSCNV combination fared far better compared to the ones only treated using the Ce NP or MSCNV group. This clearly demonstrates the synergy between anti-inflammation and immunomodulation and underlines the importance of the combined therapy for effective RA treatment. In addition, Ce-MSCNV administration prior to booster injection markedly reduced the incidence and severity of symptoms, supporting the prophylactic potential of these nanoparticles.

First author KOO Sagang stated, “One of the hardest decisions in intractable disease therapy is determining how long the treatment should be carried on. For RA, it would not be appropriate to stop treatment just because the target marker is stabilized. A safer indicator should be that the innate and adaptive components of the collapsed immune system are normalized to protect the body.”

Koo believes that the strategy adopted by Ce-MSCNVs, where different treatment mechanisms work together, provides a unique advantage in this regard. Furthermore, she predicts that a similar approach would also be applicable to other intractable, inflammatory, and autoimmune diseases for this purpose. The components within the system may also be modified. For example, other catalysts for generating ROS or other cell-derived nanovesicles could be utilized depending on the types of diseases. Overall, this study proves the potential of a hybrid nanoparticle system for the comprehensive treatment of autoimmune disease and modulation of the immune system.

Autoimmune Disease: A Food-based Approach

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An estimated 23.5 million people in the United States are living with an autoimmune disease, such as type 1 diabetes, Crohn’s disease, multiple sclerosis, rheumatoid arthritis, or myasthenia gravis. These diseases afflict women more than men and are among the leading causes of death for young and middle-aged women.

Collectively, these diseases are becoming more common around the world. Side effects from some of the medications to treat them can be harsh, so those living with these conditions may look for natural and less invasive ways to manage these diseases. But can the right diet help tame an autoimmune disease?

Learn how nutrition and your diet may help to manage some of these conditions during this free online webinar on Autoimmune Disease: A Food-based Approach.

The expert panel is comprised of:

Leigh Frame, PhD, MHS, is an assistant professor, Department of Clinical Research and Leadership, program director, Integrative Medicine Programs, and executive director, Office of Integrative Medicine and Health. Dr. Frame brings nutrition and immunity together through clinical/translational research. She has used her wide-ranging experience in biomedical research (from wet bench to clinical research) to oversee research programs, including the National Institute of Neurological Disorders and Stroke (NINDS) Parkinson’s Disease Biomarkers Program.

Susan LeLacheur, DrPH, MPH, PA-C, BS, is a professor in the Department of Physician Assistant Studies at the GW School of Medicine and Health Sciences. Dr. LeLacheur has more than 35 years of clinical experience in primary care, HIV/AIDS, and infectious disease. She is the section director for the GW PA Program’s Foundations of Medicine Gastroenterology Section. Her ongoing clinical practice at Whitman Walker Health in Washington, D.C. includes both primary and HIV care.


Lara Zakaria, RPh, MS CNS IFMCP, is an Institute for Functional Medicine Certified Practitioner, nutritionist, pharmacist and public health professional based in New York City. She combines evidence-based nutrition and complementary medicine, including positive psychology, to inspire patients to use whole food, herbs and lifestyle modification to optimize their health. Her training in drug-drug and drug-nutrient interactions also gives her a unique perspective on helping patients optimize their medication and supplement programs.

Rheumatoid Arthritis Part One – Signs and Symptoms of Rheumatoid Arthritis – Your Joints.

Rheumatoid arthritis

Rheumatoid arthritis

Welcome to the first in an ongoing series of blog posts  into the signs and symptoms of rheumatoid arthritis. This in turn is part of an informational series which we hope over time with cover the main issues associated with rheumatoid arthritis.

One of the reasons I want to cover this area in more detail is that my grandmother suffered from Rheumatoid Arthritis for many years.  Her life, I believe, could have been much easier if there was greater awareness of the realities of RA.

As you may know the symptoms of rheumatoid arthritis come in to three main categories: –

a)    Symptoms affecting the joints,

b)    Systemic symptoms or those symptoms which impact the whole body

c)    Other symptoms affecting specific organs.

Today we will focus our attention on joint symptoms.  Which are the most common symptoms (and indeed sign) of rheumatoid arthritis or RA; as it is often called.

Just by way of information a joint id defined in the Oxford English Dictionary as “A structure in the human or animal body at which two parts of the skeleton are fitted together.”

The most common symptom of rheumatoid arthritis is stiff painful and swollen joints. Typically these develop over time in joints on both sides of the body.  In many cases the joints of the hands or feet are affected first. Often other joints are affected which  include knees, elbows, wrists and shoulders among others.

The pain caused by rheumatoid arthritis is often described as “deep and aching”.

Often at its worst after periods of rest (i.e. after a long drive or waking from sleep).   It can be helps by gently moving the affected joint.   Disrupted sleep is common in people with RA because of regular waking due to pain.  This is one of the causes of fatigue in RA patients.

In the morning, after sleep, the affected joints can also feel very stiff.  This may last for some hours after waking.  The time that the stiffness lasts is often used as an example of the difference between RA and osteoarthritis.

The joint inflammation means that they, the affected joints, become “swollen, red and hot”.    As RA progresses both cartilage and bone are destroyed.  This again limits mobility and in many cases leads to deformities.

One of the aims of blog posts like this is to give our readers the opportunity to share their stories and learn from the experiences of others in the rheumatoid arthritis community!  To facilitate this it would be great if you would use the comments box below to talk about the symptoms and signs of rheumatoid arthritis.  You might care to think in terms of the following questions:-

a)    Have you been diagnosed with RA?  For how many years have you been diagnosed?

b)    What were the first signs of rheumatoid arthritis?

c)    What are now your main symptoms?

d)    What one piece of advice would you give to somebody who think they may have RA?

Thanks very much in advance.

Preventing cell death as novel therapeutic strategy for rheumatoid arthritis

Rheumatoid Arthritis: What Are the Early Symptoms?
Rheumatoid Arthritis: What Are the Early Symptoms?


A collaborative study by research groups from the University of Cologne, VIB, Ghent University, the Βiomedical Sciences Research Center ‘Alexander Fleming’ in Athens and the University of Tokyo identified a new molecular mechanism causing rheumatoid arthritis. The researchers found that death of macrophages, an immune cell type, can trigger the disease. Moreover, they discovered how the protein A20 prevents macrophage death and protects against arthritis. These findings open up new possibilities for the treatment of this debilitating disease.

Understanding arthritis

Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease that affects the joints, causing a painful swelling that eventually results in bone erosion and joint deformity. It affects 1 – 2% of the population, is very painful and severely affects the patients’ quality of life. There is no cure for RA, but the disease progression in most patients can be slowed down with anti-inflammatory drugs. The underlying molecular mechanisms that cause the disease have remained largely unclear. Understanding these mechanisms is very important and may help in developing new therapies to treat patients suffering from RA.

Cell death and inflammation

A collaboration between Prof. Manolis Pasparakis and Dr. Apostolos Polykratis (University of Cologne), Dr. Marietta Armaka (BSRC ‘Alexander Fleming’, Athens), Dr. Yoshitaka Shirasaki and Dr. Yoshifumi Yamaguchi (University of Tokyo), and Prof. Geert van Loo and Arne Martens (VIB-UGent) adds a new piece to the puzzle behind the disease. Their joint effort builds further upon earlier research at the VIB-UGent Center for Inflammation Research, which demonstrated that the protein A20 suppressed arthritis by preventing inflammation. Now the researchers show that the inflammatory response is caused by the fact that a fraction of specialized immune cells, macrophages, die by a specific inflammation-promoting type of cell death called necroptosis. The researchers were able to prevent the development of RA by blocking necroptosis.

Prof. Geert van Loo (VIB-UGent): “We could also identify why these macrophages are dying and could demonstrate the importance of a specific part in the protein A20 for the prevention of cell death and RA development.”

Dr Marietta Armaka underlines: “We revealed how the particular type of macrophage demise shapes the activation of synovial fibroblasts, a key cell type that orchestrates the destruction of cartilage and bone tissue in RA”.

New therapies

This study confirms the crucial importance of A20 in the control of inflammation, but now also shows that preventing cell death is a critical anti-inflammatory function of A20 to protect against arthritis.

Prof. Manolis Pasparakis emphasizes: “From a therapeutic perspective, this is a very important finding, since it suggests that drugs inhibiting cell death could be effective in the treatment of RA, at least in a subset of patients where macrophage death could provide the underlying trigger.”

Several pharmaceutical companies are developing new drugs to inhibit cell death, which will hopefully help to treat patients suffering from inflammatory diseases, including rheumatoid arthritis.

Rheumatoid arthritis patients affected by disabilities well in advance of diagnosis

Rheumatoid Arthritis: What Are the Early Symptoms?
Rheumatoid Arthritis:

Patients diagnosed with rheumatoid arthritis often are affected by functional disability a year or two before the disease is diagnosed, according to new Mayo Clinic research.

The results of the study, to be published in June in Mayo Clinic Proceedings, suggest that daily activities such as eating, dressing and walking are affected early in the course of the disease, and that most rheumatoid arthritis patients are affected by functional disability issues.

“This is a new finding and a finding that is quite intriguing,” says Elena Myasoedova, M.D., Ph.D., a Mayo Clinic rheumatologist and the study’s primary author. “It may reflect an accumulation of symptoms between the time of first onset and the time required for providers to actually diagnose patients.”

Also notable is that persistent excess in functional disability continued even after diagnosis and treatment, Dr. Myasoedova says, which may be due to a growing burden of mental and physical pain, use of glucocorticoids and antidepressants, increasing expectations for relief from symptoms, and other factors.

The study’s implications for additional vigilance by patients and physicians in the early stages of rheumatoid arthritis are especially relevant since May is National Arthritis Awareness Month. More than 50 million U.S. adults have some form of arthritis. About 1.5 million Americans have been diagnosed with rheumatoid arthritis, which is an autoimmune disease that most commonly affects the joints but also has an impact on other body systems.

Rheumatoid arthritis significantly affects quality of life and well-being, and is one of the most common chronic conditions associated with functional disability in the U.S.

The study is the first to quantify the long-term trends in prevalence of functional disability in rheumatoid arthritis patients, with trends noted for patients’ ages and genders, as well as the length of time that disabilities were reported and the duration of the disease after diagnosis. The study also is the first to show that functional disabilities manifest one to two years prior to a rheumatoid arthritis diagnosis.

“These findings suggest that the burden of functional disability affects most patients with RA, begins early in the disease course, and may precede RA diagnosis,” the study says.

The retroactive, population-based study accessed information from the Rochester Epidemiology Project database of medical records, and examined questionnaires from 586 patients with rheumatoid arthritis and 531 people without the disease. The prevalence of functional disability was more than twice as high in those with rheumatoid arthritis as those without. Patients with rheumatoid arthritis had a 15 percent or greater prevalence of functional disability than individuals without rheumatoid arthritis in most age groups.

Dr. Myasoedova says the study shows the prevalence of functional disability for rheumatoid arthritis patients and the importance of early treatment. “Alerting your health care provider to difficulties in daily living can assure that patients receive the help they need,” she says.

Symptoms of rheumatoid arthritis may include joint pain or swelling, though 40 percent of patients experience symptoms that don’t involve the joints, such as fatigue, fever and loss of appetite. Early rheumatoid arthritis tends to affect smaller joints first. In most cases, the symptoms occur in the same joints on both sides of the body.

Unlike osteoarthritis, which occurs as cartilage that cushions the joints breaks down over time, rheumatoid arthritis affects the lining of the joints. This leads to swelling that can cause bone erosion and joint deformity, as well as damage to other parts of the body. In addition to medical treatment, daily physical activity and a healthy lifestyle are among the best ways to relieve symptoms and overcome functional disability, Dr. Myasoedova says.