Photo: © 2015 American College of Rheumatology. Used with permission.
Localized scleroderma is a chronic autoimmune skin disorder that manifests as excess production of extracellular matrix, specifically collagen, resulting in thickening of the skin and connective tissue. Moderate to severe forms of localized scleroderma can result in significant morbidity, including pain, restricted motion, disfigurement and developmental issues. The localized areas of skin thickening may extend to underlying tissue and muscle. In children this can impair growth and development. Lesions appearing across joints can be painful, impair motion and may be permanent.
Localized scleroderma encompasses several subtypes which may be characterized based on the depth and pattern of the lesion(s). Approximately 50,000 patients in the U.S. have moderate to severe scleroderma. The moderate to severe forms of the disorder include any subtype that affects function or produces symptoms of discomfort, tightness and pain.
Current treatments for localized scleroderma include systemic or topical corticosteroids, UVA light therapy and physical therapy. There are few treatment options to address excessive collagen accumulation in the skin and connective tissue.
FCX-013 is being developed as a disease-modifying, autologous cell-based gene therapy that utilizes lentiviral vectors to deliver functional matrix metalloproteinase 1 genes (MMP-1) to patients with moderate to severe localized scleroderma. MMP-1 encodes the enzyme responsible for breaking down collagen. FCX-013 incorporates a biologic switch activated by an orally administered compound (veledimex) to control protein expression at the site of the localized scleroderma lesions.
FCX-013 is designed to be injected under the skin at the location of the fibrotic lesions where the genetically-modified fibroblast cells will produce MMP-1 to break down excess collagen accumulation. With the FCX-013 therapy, the patient will take an oral compound (veledimex) to facilitate protein expression. Once the fibrosis is resolved, the patient will stop taking the oral compound which will control further MMP-1 production.
The U. S. Food and Drug Administration has granted Orphan Drug designation to FCX-013 for the treatment of localized scleroderma. In addition, FCX-013 has been granted Rare Pediatric Disease designation and Fast Track designation for the treatment of moderate to severe localized scleroderma.
Dermal fibroblasts are collected from the patient, cultured and genetically modified to regulate collagen accumulation and then injected at the site of the localized disease.
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