Dr. Arthur DeCarlo, president and science director of Agenta Biotechnologies, has seen enough clinical cases of bone degeneration in oral and periodontal cases to be aware of what an impact bone regeneration would have in restoring health to a multitude of patients. His company is on the cusp of bringing that sort of healing into clinical studies with its efforts to advance proteoglycans, normal components in most of the body’s organs, into a new class of therapeutics. DeCarlo, a former clinician and academician and founder of Agenta, has a doctorate in biochemistry and molecular genetics. His studies of proteoglycans and their associated polymers hold the promise of speeding healing as part of the treatment protocol. “We have an enormous potential for the discovery of new drugs,” DeCarlo said. “Everything we are doing involves the potential for healing and tissue regeneration.” With a technology-based platform, DeCarlo believes the research Agenta is doing will have applications across the spectrum of medicine — from reversing sun damage to skin to treating Alzheimer’s disease. The magic bullet of myth may well be found in proteoglycans. “The smarts of the whole proposal is that we have identified the critical molecules in the natural growth and healing processes,” DeCarlo said. “With that, we can potentially make improvements on how fast broken bones or implants heal, and make improvements on cartilage and disk regeneration.” With the use of the company’s Therapeutic Proteoglycan Delivery Platform, sites in the body are targeted with the application of DNA customized specifically to help them heal. In the healing process, the targeted cells of the body create the proteoglycan. “Proteoglycans consist of two parts — the protein core and a long, sophisticated glycan chain,” DeCarlo said. “Everyone knows these molecules. There is lots of literature now showing how these are essential molecules in the delivery of growth factors. There’s potential for new blood vessel production, skin structure, cartilage and hydration. That is why our platform allows us to go in different directions.” Agenta will focus its attention first on bone healing, but the potential to take the platform in other directions drives current research. In August 2007, the National Institutes of Health awarded Agenta Biotechnologies two research grant awards, totaling $515,318. The grants provide research and development funding aimed at bone regeneration, as well as for product development in skin and gingival wound healing. The skin therapy will be a boon, not only for burn victims and wound healing, but also in opening the pipeline with cosmetic products for wrinkle repair. With demand for cosmeceutical products expected to leap to $6.4 billion by 2010, the marketability of regenerating wrinkled skin is evident. Already, the ProGo.HS1 treatment for wrinkles and skin defects is in pre-clinical trials. Agenta is in the discovery stage in another area — testing a product to coat vascular stents, devices used to open vascular circulatory pathways, in an effort to ease the body’s acceptance of the stents and reduce risk of future clot formation at the stent site. The stent market is estimated to grow to $7 billion by 2010. Preclinical trials are underway for Perl.D1, a prototype DNA product that promises significantly better bone healing. Bone was a natural area of focus for DeCarlo, who had clinical experience in trying to grow new bone around teeth and in jaws. The market for dental implants and bone grafts is estimated at more than $4.8 billion. Agenta is creating drug-like proteoglycans in a soluble form. “What’s exciting in the scientific part is that we are engineering (proteoglycans) to be enhanced,” DeCarlo said. “That is critical to the potential value of the molecules or drugs. Part of the intellectual property is that we’re working on allowing your own body to produce proteoglycans. Your body can create those glycans better than they can be created in a test tube.” DeCarlo said having the body create the healing proteoglycans would help keep drug costs lower. “It has the potential of better effect and keeps the process of synthesis out of the lab,” DeCarlo said. “We hope to take this preclinical data, which is showing positive results, and begin speaking with the FDA and get ourselves into some clinical trials.” When patients go in for periodontal treatment or oral bone grafts, support systems, such as cages or membranes, are utilized as scaffolding to hold the bone grafts in place. The proteoglycans would be placed at the site that needs to heal. Instead of using donor bone grafts, DeCarlo believes the simplest solution is the best — creating a close facsimile of bone to anchor the treatment area. “Synthetic bone graft material is the future,” DeCarlo said. “The material is almost like porcelain with very inert calcium phosphate. That seems to work pretty well, and that’s why we are perfectly placed to bioactivate the bone grafts with Agenta technology. Bioactivation will promote those cells to convert to bone-growing cells. That could be in combination with other technologies, and healing is five times faster, potentially. That’s where we are heading.” While the drug could be administered orally, DeCarlo hopes the FDA will see the need for it to be placed locally, at the wound site. In the human body, disks and cartilage are comprised, in large part, of proteoglycans, making them another target area for therapeutic proteoglycans. “I already have degenerating disks and have had surgery,” DeCarlo said. “I can’t wait until we have a chance to test this in disk regeneration. We would probably take the bioactivating substance and inject it in the pulp of the disk and repeat over a period of a year. The disk should increase in size and structure and regenerate.” Having assembled a team with experience in science and clinical work, DeCarlo believes he’s created an ideal convergence of forces that can bring the ideas to fruition soon. “We plan on an FDA trial and hope to start at the beginning of 2010,” he said. “We have to have approval by then, and data. That’s when the business plan really says we should be in clinical trials.’ DeCarlo’s fascination with the science, combined with his clinical experience has been crucial in creating an equation for healing. “Seeing patients is a great honor and work in academics is a great honor, and I’ve done these,” he said. “But I think the fastest way to create useful products is to take that step into the biotechnology industry. I think that propelled all the work to put this together and make it happen. Life is always a circumstance of coincidence and timing and that’s where we are now.” March 2008