Excessive collagen deposition in the skin is a hallmark of scleroderma. Currently there are no safe and/oreffective therapies. Excessive accumulation of collagen is responsible for the markedly thickened and hardfeel to the involved skin of scleroderma. Therefore, a therapy that can safely enhance collagen breakdownis expected to improve it. We have accumulated solid evidence that UV irradiation of human skin activates acomplex signaling cascade in cells that ultimately results in a several fold increase in the amount of matrixmetalloproteinases (MMPs) with consequent degradation of collagen, while simultaneously inhibiting newprocollagen synthesis. Thus, by removing already present dermal collagen and suppressing production ofnew collagen, UV is capable of causing a net collagen loss in human skin. As a phototherapeutic devicehowever, both UVB (290-320nm) and UVA1 (340-400nm) have significant limitations. More energetic UVBis associated with sunburn reaction, and its carcinogenic potential is well established. UVA1 is safer andbetter tolerated by human skin. However, we have learned that both natural and UV-induced skinpigmentation are effective blockers of UVA1. Scleroderma affects subjects with all levels of skinpigmentation (types I-VI). An antifibrotic treatment modality that is not influenced by skin color will offer asignificant medical advancement, especially in darkly pigmented African American, Hispanic, Indian, or Asianpatients (types V&VI). Our preliminary data indicate that infrared irradiation (IR; specifically 700-4,000nm)that raises skin surface temperature to 41 degrees C is capable of safely inducing MMPs and inhibiting procollagenirrespective of human skin pigmentation. Thus we hypothesize that IR will also improve scleroderma andother fibrotic diseases. We propose to 1) fully characterize the ability of IR to reduce collagen in normal skin,and 2) obtain preliminary data of the IR effect on scleroderma skin. The data generated with the assistanceof RDCC will form the basis for an application to the NIH to fund a multicenter IR therapeutic trial inscleroderma.
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