After spending the last few years developing a cell-mediated therapy for treating degenerative joint diseases, privately held TissueGene Inc. is ready to move into Phase I testing with its first product, TG-C, in patients with osteoarthritis of the knee.

TG-C combines a cell therapy approach with TGF-beta, a growth factor protein extensively investigated by TissueGene President and CEO Kwan Lee, who founded the company in 1999. While TGF-beta's capacity as a regenerative protein has long been established, Lee's research focused on how to get the growth factor to the damaged tissue.

"The problem with TGF-beta as a therapeutic molecule is that its half-life is extremely short - we're talking minutes to hours," said Kelly Ganjei, vice president of business development for Gaithersburg, Md.-based TissueGene.

Though other growth factors, such as bone morphogenic protein 2 (BMP-2), can be embedded into matrices to provide a degree of sustained release, "this has not been possible with TGF-beta," he added.

But Lee found a promising solution in the field of cell-mediated therapy, an approach that is being investigated by several companies in cancer and other life-threatening diseases.

In the case of TGF-beta, a cell therapy approach could generate "a sustained release, as well as localized expression, which is exactly what [Lee] wanted to do," Ganjei said, adding that Lee then went on "to design our own animal models for cartilage repair."

Existing cartilage regeneration technologies for osteoarthritis generally involve multiple surgical procedures. TissueGene's technology involves the insertion of the therapeutic growth factor gene into cells, then culturing and stabilizing those cells before injecting them in the damaged tissue site via a hypodermic needle. The genetically modified cells would head straight for the injured site to provoke regeneration.

"After that, it was a race to bring our first product, which is a chondrocyte cell modified to express TGF-beta, into Phase I," Ganjei said, and the company received the FDA's go-ahead last month to conduct a Phase I trial in patients who have opted for total knee arthroplasty.

While the primary objective is safety, the study's design offers TissueGene "a unique situation" to observe the histopathology of the patient's tissue, Ganjei said.

"Four weeks prior [to the surgery], the patients will get an injection of our cells, and then, at the time of the surgery, we will actually get to harvest the resected knee tissue," he told BioWorld Today. "Those resected knee tissues will be able to provide us with some ability to measure what's really going on in these patients so we can see whether it's taking hold at the site of the injury."

The company expects a short trial and results "much sooner than with other standard clinical protocols," Ganjei said. "The goal is then to design a Phase II clinical plan based on those results."

He added that the company believes TG-C could have "clinical applicability in multiple osteoarthritis indications."

TissueGene has no plans to market and sell the product itself, and Ganjei said the firm is in discussions with potential partners.

"We're really looking for a partner who has an existing presence in the orthopedic space and has a vested interest in the biologics market," he said.

Beyond that TG-C, TissueGene is developing candidates for bone healing, including osteoporosis or diabetic fractures, and nerve healing. All would use the same approach: the injection of cells that have been modified genetically to express a growth factor. There also is the potential of using other products, such as biphosphonates, which could open the door to other partnerships and co-development opportunities down the road.

TissueGene has 15 employees in the U.S., with another 12 at its sister company in South Korea, where many of the animal studies are conducted.

To date, the company has raised $17 million in a Series A round, with hopes to add another $5 million or $6 million this year.