PhD defence Katrin Agnes Münzebrock

Keywords: Arthritis, Chronic low back pain, mRNA treatment

"mRNA delivery for joint and intervertebral disc regeneration"

Osteoarthritis and chronic low back pain are common wear-related disorders of the musculoskeletal system. To date, there is no treatment available that can stop degeneration or repair tissue. Instead, only the symptoms, such as pain and immobility, can be somewhat reduced with pain medication or physical therapy. In extreme cases, surgery can provide relief, but not repair to the original state.This thesis investigates the use of mRNA-based therapies for the treatment of osteoarthritis and intervertebral disc degeneration. mRNA has great potential due to its safety, versatility, and long-lasting effect, but requires efficient delivery systems due to its instability. Therefore, the applicability of nanoparticles for mRNA delivery in joints and intervertebral discs was investigated. The results show that nanoparticles can effectively deliver mRNA to various relevant cell types, leading to successful protein production. Unfortunately, there was no demonstrable positive effect in a rat model of osteoarthritis. In addition, this thesis shows that ultrasound could improve the penetration of mRNA nanoparticles in simple models of cartilage. Further research and improvement of research models is needed to help patients in the future and repair cartilage and intervertebral discs using mRNA-based therapies. 

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