Drug amount regulation by implanted SMART

Nandini Pharasi, Jaypee Institute of Information Technology

When implanted in mice, the gene-modified cells will produce a biological medicine that can cure inflammation, allowing the researchers in St. Louis to create therapies for rheumatoid arthritis that have minimal adverse effects. Rheumatoid arthritis, a severe illness that affects about 1.3 million individuals in the United States, is the ultimate aim of the study team. In a mouse model of rheumatoid arthritis, the modified cells decreased inflammation and avoided bone degradation. 

Injections or infusions?

Researcher Dr Farshid Guilak is a professor of orthopaedic surgery at Mildred B. Simon School of Medicine said “Injections or infusions of anti-inflammatory biologic drugs are often used to treat rheumatoid arthritis patients, but these drugs can cause significant side effects if they are administered for long enough and at high enough doses to have beneficial effects.  

A new study using CRISPR-Cas9:

Teams coordinated tactics to treat rheumatoid arthritis in their new study. In order to alter the genes in stem cells, we employed CRISPR technology. By seeding the cells on woven scaffolds, we generated a tiny cartilage implant that we implanted in mice. Using this method, the cells may stay in the body for a long period and produce a medication anytime there is an inflammatory flare-up. Their earlier work involved creating cartilage-forming frameworks, which they coated with stem cells and then inserted in joint spaces for cartilage growth. When cartilage genes are triggered by inflammation, CRISPR-Cas9 technology is used to modify the genes in those cells so that they produce medicines in response. Engineered cartilage cells are injected in such a way that they don’t float away after a few days, and may live for months or more. Because the medication inhibits interleukin-1 (IL-1), a chemical that causes inflammation in arthritis by activating inflammatory cells in the joint, the treatment decreases inflammation in joints CRISPR-Cas9 genome editing technology was utilized by researchers to create cells that produce a biologic medicine in response to inflammation. A biologic medicine is released by cells that have been residing under the skin or in a joint for months,” explained Guilak.

 Anakinra, an immunosuppressant medication that binds to IL-1 and inhibits its action, was used in this case. Because it has a short half-life and does not remain in the body for long, this medication is not commonly used to treat rheumatoid arthritis. The medication decreased inflammation and avoided bone deterioration found in rheumatoid arthritis mice, according to the research.

‘Rheumatoid arthritis patients suffer from bone degeneration, which is not addressed by current biologics.’ A new technique of bone deterioration reduction was identified when we used imaging equipment to examine the animal’s bones in great detail. Despite the fact that biological agents have changed the treatment of inflammatory arthritis, the continuous administration of These drugs usually results in side effects, including an increased risk of infection, which is why we are so pleased to note that the first author and co-author, Dr. Yunrak Choi. When it comes to working with arthritis patients, the notion of administering such medications essentially on-demand in response to arthritic flares is highly appealing since it might reduce side effects associated with ongoing high-dose administration of these treatments. “

For example, if one arthritis medication works better in a certain patient than another one, researchers might use CRISPR-Cas9 gene editing to create cartilage cells to develop customized therapies. Other inflammatory arthritis diseases, such as juvenile arthritis, which affects 300,000 children in the United States, might benefit from the technique. A number of patients must administer these drugs by injecting themselves on a regular basis, while others must visit a doctor every few months to receive an infusion of one of these biologic drugs. However, in this study, researchers have shown that living tissue can be used as a drug delivery system. As a result, these cells are able to detect abnormalities and respond by manufacturing drugs.

Conclusion:

This helps us understand why certain biologics may have a limited impact on inflammatory arthritis, as well as how they work. Instead of failing to attach to the correct target, the short-term effects of an injected medication pale in comparison to the automatically regulated drug amounts produced by implanted SMART cells. Using CRISPR-Cas9 and stem cells, the researchers are continuing to explore, even creating SMART cells that might produce more than one medication in response to diverse inflammatory stimuli.

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References:

1. Choi, Y.-R., Collins, K. H., Springer, L. E., Pferdehirt, L., Ross, A. K., Wu, C.-L., Moutos, F. T., Harasymowicz, N. S., Brunger, J. M., Pham, C. T. N., & Guilak, F. (2021). A genome-engineered bioartificial implant for autoregulated anticytokine drug delivery. Science Advances. https://www.science.org/doi/abs/10.1126/sciadv.abj1414
2. Medicine, W. U. S. of. (n.d.). Rheumatoid arthritis treated with implanted cells that release drug. Retrieved September 3, 2021, from https://medicalxpress.com/news/2021-09-rheumatoid-arthritis-implanted-cells-drug.html

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