Localized Scleroderma: What’s the Way Forward?

(DGIwire) – A large number of medical conditions have names rooted in Latin terms. One example is “scleroderma”— “sclero” means “hard” and “derma” means “skin.” But hardening skin is just one of many symptoms of localized scleroderma, a chronic autoimmune disease, which has no known cause and no cure. Stiff joints, digestive issues, lung scarring, kidney failure—all can occur and can sometimes be fatal, according to the Scleroderma Foundation.

Localized scleroderma manifests in a number of different forms or subtypes, which includes the linear subtype, totaling slightly less than 200,000 people in the United States. The U.S. population of patients who are considered to have severe localized scleroderma is estimated to be approximately 90,000, according to research published in Archives of Dermatology.

“Current treatments for localized scleroderma—including systemic or topical corticosteroids, UVA light therapy and physical therapy—only address the symptoms of the disorder,” says John Maslowski, President and Chief Executive Officer of Fibrocell, a gene therapy company. “Now, we are pursuing gene therapy as a potential new approach to improve the standard of care for this disease.”

To this end, Fibrocell is developing FCX-013, the Company’s gene therapy candidate for the treatment of moderate to severe localized scleroderma. FCX-013 is an autologous fibroblast cell genetically modified using lentivirus and encoded for matrix metalloproteinase 1 (MMP-1), a protein responsible for breaking down collagen. FCX-013 incorporates Intrexon Corporation’s proprietary RheoSwitch Therapeutics System®, a biologic switch activated by an orally administered compound to control protein expression at the site of 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 to facilitate protein expression. Once the fibrosis is resolved, the patient will stop taking the oral compound, which will control further MMP-1 production.

Fibrocell’s proprietary autologous fibroblast technology takes advantage of the properties of these cells. In addition to being ubiquitous in the body, fibroblasts can be isolated from the skin and grown in culture, where they can be genetically modified. They serve as a unique delivery vehicle, with capabilities for localized (vs. systemic) delivery to gene targets in the skin and connective tissue.

FCX-013 is currently in preclinical development for the treatment of moderate to severe localized scleroderma. The U.S. Food and Drug Administration has granted Orphan Drug Designation to FCX-013 for the treatment of localized scleroderma, which includes linear scleroderma.  In addition, FCX-013 has been granted Rare Pediatric Disease Designation for the treatment of moderate to severe localized scleroderma, including the linear subtype.

“With no FDA-approved therapies available, we believe controlled gene therapy through FCX-013 offers promise to be a first-in-class treatment to address the high unmet medical need of patients suffering from this chronic and often debilitating disease,” adds Mr. Maslowski.