TissueGene, Inc. (GAITHERSBURG, Md.), a privately-held biopharmaceutical company advancing a pipeline of regenerative medicine therapeutics, including a proprietary cell technology with applications in the treatment and regeneration of damaged tissues such as cartilage and bones, announced the initiation of a phase I clinical trial of the company's cell-mediated therapy, TissueGene-C (TG-C). The trial will evaluate a single dose of TG-C in patients with degenerative arthritis of the knee joint refractory to existing therapies, who are scheduled for total knee arthroplasty. According to the results obtained in animal models, TissueGene's technology is applicable to major (full-thickness) cartilage defects as opposed to only minor (partial-thickness) defects, and the technology produces fully integrated hyaline cartilage, instead of partially integrated hyaline cartilage with fibro-cartilage formations.

TG-C is based on the infection of primary chondrocytes with a retroviral vector expressing transforming growth factor-beta1 (TGF-beta1), followed by the intra-articular injection of the modified cells. The vector is a MoMSV/MoMLV hybrid-based retroviral vector, which is devoid of gag, pol or env gene sequences, such that replication competent retrovirus is not generated by recombination with homologous sequences in a viral packaging system. The vector contains a CMV major immediate early gene promoter/enhancer driving expression of the TGF-beta1 gene.

TissueGene developed TG-C to regenerate cartilage in patients suffering from degenerative arthritis such as osteoarthritis (OA) of the knee. As an alternative to other methods of cartilage repair, TG-C will involve minimally invasive injections for heterologous applications versus a surgical approach. For autologous applications, one surgery may be required to collect chondrocytes from the patient. Other techniques currently involve multiple and often invasive surgical procedures and have mixed results. In preclinical animal studies of TG-C, damaged cartilage in knee joints in rabbits and dogs has been effectively repaired through the injection of the genetically modified cells. Cells were injected into rabbit achilles tendon and knee joints with artificially-made cartilage defects. Intratendinous injections were performed to determine the optimal concentration for in vivo expression. The partially defected cartilage model simulates degenerative arthritis of the knee joint. The partial cartilage defect treated with the cell-mediated gene therapy procedure was covered by newly formed hyaline cartilage, which indicates that the cells survived and stimulated matrix formation in this area. Completely denuded cartilage areas were covered by fibrous collagen.

The company's technology can be used to treat and repair damaged tendons, ligaments, cartilage and bones. Initially, the Company is focusing on providing a cure for OA. Expanding into other clinical areas, Tissuegene will focus on similar applications in sports medicine (eg, ligament and tendon repair) and degenerative disorders such as diabetic fracture healing and osteoporosis.

— A. Techman

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