Vitamin D Nanoparticles Show Promise in Rheumatoid Arthritis Treatment

Nanoparticles designed to slow the progression of rheumatoid arthritis (RA) and lessen the severity of flare-ups have been developed and tested using human blood and mouse models with rheumatoid arthritis-like disease, according to a study led by researchers from the University of Southern California and other institutions (1^✔ ✔Trusted Source
Immunomodulatory Nanoparticles Enable Combination Therapies To Enhance Disease Prevention and Flare Control in Rheumatoid Arthritis

Go to source). While current treatments help manage symptoms in most people, they do not prevent the disease’s onset or eliminate painful flares.

Joint Tissue Inflammation and Limitations of Current Treatments

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.

Nanoparticle Composition and Aggrecan Protein Fragment

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.

Reduced Immune Response in Human Blood Samples

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.

Combination Therapy Delays Disease Onset in Mice

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.

Reference:

1. Immunomodulatory Nanoparticles Enable Combination Therapies To Enhance Disease Prevention and Flare Control in Rheumatoid Arthritis - (https://pubs.acs.org/doi/10.1021/acscentsci.5c00723)

Source-Eurekalert