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Abstract

The invention uses the existence of tissue-specific telopeptide lysyl hydroxylases, enzymes that hydroxylate lysine residues of the telopeptides of collagen, and the discovery that collagen molecules cross-linked by hydroxyallysine (derived from telopeptide hydroxylysine) are less susceptible to degradation/turnover than collagen molecules cross-linked by means of allysine (derived from telopeptide lysine) due to a different intrafibrillar packing of said collagen molecules. Further, the invention contemplates that one of the characteristics of collagen in scars and other fibrotic tissues is an increase in hydroxyallysine derived cross-links (making the collagen less susceptible to proteolytic breakdown), that this increase in hydroxyallysine cross-links is due to increased levels of telopeptide lysyl hydroxylase, and that telopeptide lysyl hydroxylase plays an important role in the excessive accumulation of collagen in fibrosis/scarring. Still further, the invention relates to methods using said knowledge for the treatment of fibrosis/scarring by inhibiting telopeptide lysyl hydroxylase activity or inhibiting telopeptide lysyl hydroxylase translation/transcription in order to decrease selectively hydroxyallysine cross-links (leaving the allysine cross-link route intact).

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First Claim