Targeted delivery in scleroderma fibrosis

Abstract Systemic sclerosis (SSc) is considered one of the most challenging and difficult to treat among rheumatic disorders, due to its severity, multiorgan manifestation and different outcomes. It manifests fibrosis in different organs, mostly in skin and lungs. The skin fibrosis expression is considered the first sign of the disease and usually it is followed by internal organ fibrosis. An aberrant immune system activation seems to relate to the expression of the disease, but even environmental influences and dysregulation of many molecules signalling pathways are involved in the development of the disease. Current therapies are limited and characterized by multiple side effects: systemic route is the elective administration route, which decreases patient adherence to the therapy, as they are often already bothered by pain and disfigurement. Treatments available are organ-based, originally indicated for other conditions and there is no therapy available to reduce the fibroblast population size within existing fibrotic lesions. Disease-modifying therapies or immunomodulatory agents that are highly effective in other rheumatic diseases have shown disappointing results in SSc. There are thus no standardized and effective treatments for this disease, and there are even unanswered questions related to the insurgence of the pathology and all the mechanisms involved. An ideal approach could be considered “targeted therapy” that will be an increasingly attainable objective insofar as our understanding of the disease improves. The advantages in identifying the molecule and the signalling pathways involved in the pathology have helped to find some novel compounds for the therapy of scleroderma fibrosis or following innovative uses for already-approved drugs, corroborated by many clinical studies.