Chondrogenic and Osteogenic Inducing Molecule ( 98063)

A new family of polypeptides, called amelogenins, with activities similar to the bone morphogenetic protein family to potentiate tissue mineralization in vivo, has been identified and characterized. These polypeptides, which are translation products of particular gene splice variants of the amelogenin gene, are useful in tissue and bone regeneration. Furthermore, the amelogenins are useful in the treatment of regeneration of dentin and in mineralization of the dental pulp, and possibly in cementum regeneration.

BACKGROUND: Bone morphogenic proteins (or BMPs) have been studied extensively for their ability to promote osteogenesis or bone development. It has been observed that specific amelogenin isoforms can also initiate bone and cartilage formation, hence may be an alternative to BMPs. The full length amelogenin is a structural protein, believed to play a role in tooth enamel formation by stabilizing newly formed enamel crystals and inducing the crystal’s subsequent growth. Two small isoforms produced normally as products of the alternative splicing of the amelogenin gene (the A+4 and A-4 isoforms) are signaling molecules that promote sulfate incorporation into proteoglycan and the production of cartilage type II collagen in embryonic mouse fibroblasts in vitro, and induce ectopic mineralization when implanted in bioabsorabable matrices in vivo.

These isoforms have been further analyzed in in vitro and in vivo experiments. Purified recombinant polypeptides corresponding to the A+4 and A-4 isoforms have the same effect as the tissue extracted proteins, and are able to initiate the chondrogenic phenotype in embryonic mouse fibroblasts in vitro, and induce ectopic mineralization when implanted in bioabsorbable matrices in vivo. When these recombinant peptides are implanted in dentin defects in vivo, regeneration of the dentin bridge (A+4), or a generalized mineralization of the pulp cavity (A-4), depending on the circumstances of the implant is observed. Further studies suggest that these isoforms may induce cementum attachment in teeth and promote collagen for tissue regeneration.

STAGE OF DEVELOPMENT: U. S. Patent No. 6,677,306 has issued and Northwestern University is looking for a corporate partner to bring this technology to market.

For further non-confidential information, please see:

1. The Journal of Biological Chemistry, Volume 275 (62), pp 41263-41272, December 29, 2000.

2. Bioactive molecules and the future of pulp therapy. American Journal of Dentistry 16: 66-76, 2003

Type of Offer: Licensing

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