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Researchers discover molecular mechanism behind vertebral column degeneration

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Italian researchers at the Catholic University of Sacred Heart in Rome have found a molecular mechanism responsible for degeneration of the vertebral column, according to research published in Spine.

According to a Catholic University of Rome news release, the researchers also developed an experimental drug to inhibit the degenerative mechanism, testing it successfully in mice. The drug works by blocking the molecule NF-kB.

“Our study shows that by inhibiting NF-kB, we can stop spine degeneration,” study author Luigi Aurelio Nasto, MD, stated in the release. “Drugs that turn off or even only partially inactivate NF-kB could be used to prevent the degeneration of intervertebral discs in patients.”

Nasto and his group performed systemic inhibition of NF-kB activation in a cohort of mice, measuring and analyzing disc cellularity, total proteoglycan content and proteglycan synthesis within the inhibited mice and the same factors in a group of untreated control mice.

Blocking occurred either genetically, through deletion of the proper allele, or through use of a drug that blocked formation of an NF-kB upstream activator.

According to the release, the authors found high concentrations of NF-kB caused degeneration within the intervertebral discs. The molecule is a transcription factor that modulates the activation of specific target genes, the release noted, adding hat the researchers found NF-kB activates many genes related to inflammation while turning off anti-inflammatory protective genes. “In our study, we developed a specific drug, called NBD peptide, able to specifically inhibit the deleterious action of NF-kB,” study author Enrico Pola, MD, stated in the release. “We hope to develop other selective inhibitors of NF-kB to slow the degeneration of intervertebral discs.”

Reference:

• Nasto LA, Seo HY, Robinson AR, et al. Inhibition of NF-kB activity ameliorates age-associated disc degeneration in a mouse model of accelerated aging. Spine. 2012. doi: 10.1097/BRS.0b013e31824ee8f7

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