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Home  > Press Release  > Treatment of intervertebral disk disease by administration of messenger RNA encoding a cartilage-anabolic transcription factor

Treatment of intervertebral disk disease by administration of messenger RNA encoding a cartilage-anabolic transcription factor

Abstract

Intervertebral disk (IVD) degeneration is often associated with severity of lower back pain. IVD core is an avascular, highly hydrated tissue composed of type II collagen, glycosaminoglycans, and proteoglycans. The disk degeneration is not only a destruction of IVD structure, but is also related to a disorder of the turnover of the disk matrix, leading the jelly-like IVD core to be replaced by fibrous components. Here we present a disease-modifying strategy for IVD degenerative diseases by direct regulation of the cells in the IVD using mRNA medicine, to alter the misbalanced homeostasis during disk degeneration. When mRNA encoding a cartilage-anabolic transcription factor, runt-related transcription factor-1, was administered to a rat model of coccygeal disk degeneration using a polyplex nanomicelle composed of polyethylene glycol – polyamino acid block copolymers and mRNA, the disk height was maintained to a significantly higher extent (≈ 81%) compared to saline control (69%), with prevention of fibrosis in the disk tissue. In addition, the use of nanomicelles effectively prevented inflammation, which was observed by injection of naked mRNA into the disk. This proof of concept study revealed that mRNA medicine has a potential for treating IVD degenerative diseases by introducing a cartilage-anabolic factor into the host cells, proposing a new therapeutic strategy using mRNA medicine.

Journal Article

JOURNAL:
Molecular Therapy - Nucleic Acids

TITLE:
Treatment of intervertebral disk disease by administration of messenger RNA encoding a cartilage-anabolic transcription factor

DOI:
https://doi.org/10.1016/j.omtn.2019.02.012

Correspondence to

Keiji ITAKA,M.D., Ph.D.,Professor
Department of Biofunction Research
Institute of Biomaterials and Bioengineering,
Tokyo Medical and Dental University(TMDU)
E-mail:itaka.bif(at)tmd.ac.jp

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