Cell Therapy for Localized Scleroderma Can Reverse Fibrosis in Mice

A cell therapy based on injected genetically modified human skin cells and a pill that activates a protein has the capacity for breaking down fibrosis in localized scleroderma — at least in mice.

Fibrocell and Intrexon will present preclinical data on their investigational cell therapy FCX-013 for the treatment of localized scleroderma at the 20th Annual Meeting of the American Society of Gene & Cell Therapy May 10-13 in Washington, D.C.

The presentation, “Development of an Autologous Gene-Modified Cell Therapy for the Treatment of Localized Scleroderma” — part of the Somatic Stem Cell Therapies session — describes the treatment and its effects in mice.

The skin cells used, called fibroblasts, are cells that contribute to fibrosis in scleroderma patients. While developers envision these cells being taken from a patient’s own skin, they used normal fibroblasts for the experiments.

FCX-013 is composed of two parts: fibroblasts that are genetically modified to secrete a protein called MMP1 (matrix metalloproteinase 1) and a biological switch in the form of a pill. In addition to the MMP1 gene, researchers add a stretch of DNA that can be used to control the activity of the gene.

The cells are injected beneath the skin in the location of a fibrotic skin lesion. When the gene is active, it produces plenty of MMP1 that is released from the cells. The protein then breaks down excessive collagen in a fibrotic skin lesion. But it can only do so if patients also take a pill with the compound veledimex, which activates the gene. Intrexon, which developed this activation system, calls it the RheoSwitch Therapeutic System.

Testing the system in mice with skin fibrosis, researchers noted that one injection of cells followed by daily treatment with veledimex significantly reduced fibrosis, assessed through skin thickness measurements. The underlying muscle layer also became thinner.

Their data also indicated that relatively low levels of MMP1 were sufficient to reverse fibrosis.

The research team also tested whether the switch was really working by measuring blood levels of MMP1 in mice who did and did not receive veledimex after cell injection. The protein could only be detected in mice that received veledimex.

The U.S. Food and Drug Administration (FDA) has granted FCX-013 orphan drug status for the treatment of localized scleroderma. The label intends to provide economic incentives for drug developers focusing on therapies for rare diseases.

The two companies are currently running pharmacology and toxicology studies that will enable them to move into human clinical trials.