SBIR/STTR Award attributes
Abstract Systemic sclerosissclerodermaSScis a chronic connective tissue disease in which lung fibrosis is the most frequent cause of deathSSc and idiopathic pulmonary fibrosis are the two most common disease that falls under the interstitial lung diseasesILDa grouping of devastating diseases in which lung fibrosis leads to progressive shortness of breatha very poor quality of lifeand death within a few yearsAutologous local Mesenchymal Stem CellMSCinjections have been shown to have a short term beneficial effect on SSc patients by healing ulcersreturning feeling to the fingersand enhancing facial skin elasticity and the ability to open and close the mouthIn contrastbeneficial effects of MSC therapy on lung fibrosis have not been reportedCaveolinis a promising therapeutic target in fibrotic diseasesThe effects of caveolindeficiency in cells and in animals can be reversed using the CaveolinScaffolding Domain PeptideCSDWe have shown that many cell types from SSc patientsfibroblastsmonocytesMSCsare deficient in caveolinleading to collagen overexpression by fibroblastshypermigration by monocytesand myofibroblast differentiation at the expense of adipocyte differentiation by MSCsWe have shown analogous effects in a mouse model in vivoCSD has beneficial effects on lung and skin fibrosis including reversing the thinning of the subcutaneous fat layerthis thinning is also observed in SSc patientsRecentlywe have shown that the beneficial effects of MSCs and full length CSD on lung fibrosis are synergistic and thatsubdomains of CSD are as effective as full length CSD in various in vitro and in vivo assayBased on these studieswe willAimIdentify a subdomain of CSDlead compoundwith the same activity as full lengthamino acid CSD in synergizing with MSC therapy in having a beneficial effect on lung fibrosisAimDevelop stabilitysolubilityand pharmacokinetic data for each candidate subdomain to determine if any of these peptides has significant advantages over the othersThese studies will help predict a human dose level and the safety margin we will have in human studiesIn summarythe improvements in MSC therapy that will result from the completion of this project will have great commercial potential because of their ability to enhance the quality of life and lifespan of SSc patients Narrative Systemic sclerosisSScis a chronic connective tissue disease in which lung fibrosis is the most frequent cause of deathOur long term objective is to develop an optimal version of the CaveolinScaffolding Domain PeptideCSDthatin combination with the injection of Mesenchymal Stem CellMSCsstops the progression of SSc lung disease
