(Press-News.org) As a chronic condition, rheumatoid arthritis (RA) can’t be cured, so treatment focuses on managing the disease and controlling its progression. Although current treatments help control RA symptoms in most people, they cannot prevent the onset of RA or painful flare-ups. Now, researchers publishing in ACS Central Science have developed nanoparticles that could slow disease progression and reduce flare severity, based on results from tests with human blood and mice models with RA-like disease.
For a person diagnosed with RA, their immune system attacks tissue that makes up the joints, causing inflammation, swelling and pain. However, as the disease progresses, serious cartilage and bone damage can occur if left uncontrolled. Disease-modifying anti-rheumatic drugs (DMARDs) such as abatacept reduce disease activity and slow progression of symptoms, but most people taking DMARDs still experience symptom flare-ups. And for people with pre-RA, who have detectable levels of RA autoantibodies but don’t have symptoms, there are no approved treatments to prevent disease onset.
In previous research published in ACS Nano, a research team led by Nisarg Shah and Nunzio Bottini reported that calcitriol-loaded nanoparticles, termed CLNP, help regulate immune responses and decrease inflammation for autoimmune diseases in joints. The nanoparticles were made of a polymer containing calcitriol, the active form of vitamin D3. In addition, the researchers attached a small protein fragment to the CLNP. The fragment is derived from aggrecan (Agg), a protein in the joints that the immune system can mistakenly attack in RA. To expand on their previous work, the researchers wanted to see if the modified nanoparticles could treat RA flares and pre-RA.
First, the researchers improved the nanoparticle formulation, focusing on size and stability. This helped ensure that the nanoparticles were free from any contaminants and could be frozen for a month without any damage.
The researchers then confirmed that the nanoparticles regulate dendritic cell activity, a type of immune cell responsible for initiating inflammation and flare-ups in RA. To test the nanoparticles’ effectiveness, the researchers took blood samples from people with and without RA and treated the samples with Agg-CLNP. Agg-CLNP reduced dendritic cell activity which, in turn, reduced the cell’s immune response. By suppressing the immune response, Agg-CLNP could help alleviate RA symptoms such as inflammation and swelling.
The researchers also tested Agg-CLNP in a mouse model for RA. Agg-CLNP delayed inflammation and swelling when administered as a preventative treatment, but it had little effect when administered after the onset of RA. In a subsequent study, when the researchers gave both abatacept and Agg-CLNP to the mice, the combination delayed disease onset and reduced joint inflammation, swelling and bone damage. Additional tests in mice also showed that Agg-CLNP reduced future RA flare severity when administered after corticosteroid treatment, which is often used to provide symptomatic relief. The researchers say that these results highlight Agg-CLNP as a potential therapeutic to address current limitations in RA treatments.
The authors acknowledge funding from the National Institutes of Health, the Arthritis National Research Foundation, a Hellman Fellowship, the Swedish Society for Medical Research, the Swedish Research Council, the Foundation of King Gustaf V’s 80th Anniversary, and the IngaBritt and Arne Lundberg Research Foundation.
The study’s experimental approach was approved by the Internal Review Board at Cedars-Sinai Medical Center.
The paper’s abstract will be available on Aug. 6 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acscentsci.5c00723
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