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Please Note: The technology listed below is not available to the public at this time. This technology requires further development before it is ready for the marketplace. T he VA is currently in the process of identifying potential companies who may be interested to commercially develop the technology. The VA inventors are available to collaborate with interested companies through a Cooperative Research and Development Agreement (CRADA). Through cooperative research initiatives such as these, it is our hope and goal that commercial products will be fully developed and made available to benefit veterans and others.
VA TECHNOLOGY OPPORTUNITY BRIEF
Therapeutic Application of PAPP-A
(#06-062)
OPPORTUNITY
The Department of Veterans Affairs (VA), is seeking a commercialization partner to license and/or further develop this technology through a Cooperative Research & Development Agreement (CRADA) in order to expedite bringing it to market.
BACKGROUND
The current treatments for osteoporosis are dominated by anti-resorptive agents, where the strategy is to decrease or stop rapid bone loss. However, there is a market need for therapeutics that are capable of improving the new bone growth, especially in cases where the condition has deteriorated. This strategy is thought to be more promising for increasing bone density and thus preventing fractures. PAPP-A, Pregnancy-Associated Plasma Protein A, an anabolic agent, has the potential to address this need. Similarly, rheumatoid arthritis patients suffer from painful bone loss in their joints as a result of the body's inflammatory response. PAPP-A, directed to the joint regions, can stimulate bone growth, which would help maintain proper joint architecture and decrease this pain. Sarcopenia, the degenerative loss of skeletal muscle mass, is primarily treated by life style changes and preventative measures, such as muscle resistance exercise and a protein rich diet. PAPP-A stimulation of myoblast proliferation can provide another effective strategy for treating sarcopenia.
TECHNOLOGY OVERVIEW
Insulin-like growth factors, IGF-I and IGF-II, play a pivotal role in the regulation of growth and development. Past studies demonstrate that local or systemic treatment with the IGF-I peptide can promote bone formation, muscle regeneration, angiogenesis, and peripheral nerve regeneration. Although these IGFs may be a promising new method for treatment in a variety of disorders, one major barrier for their implementation is the inhibition of IGFs by several IGF-binding proteins (IGFBPs) in vivo. Therefore, increased degradation of these inhibitory IGFBPs represents a potentially better alternative treatment for metabolic diseases, where IGF deficiency is involved in the pathogenesis. PAPP-A has recently been identified as a protease that significantly degrades IGFBP-4 and IGFBP-5. Therefore, the present invention seeks to use PAPP-A as a treatment to induce bone growth, muscle regeneration, angiogenesis, and peripheral nerve regeneration by increasing the population of active IGFs.
TECHNICAL MERIT:
Recent transgenic mouse studies by the inventors support the idea that PAAP-A is a potent anabolic factor for promoting bone formation and vascularization. Use of PAAP-A in these studies performed better than IGF-I or any other known growth factor in promoting bone formation and vascularization. The inventors seek to develop PAPP-A as a therapy, as either a recombinant PAPP-A protein or PAPP-A gene transfer, for treatment of pathophysiological disorders including osteoporosis, sarcopenia, vascular diseases, bone and soft tissue injuries. These treatments can be delivered locally or systemically, depending on the pathological conditions. Additionally, IGF-I therapeutic efficacy may be enhanced when co-administered with PAPP-A.
FOR MORE INFORMATION CONTACT:
Jeffrey Moore, Ph.D.
Technology Transfer Program
Department of Veterans Affairs
Office of Research & Development (12TT)
810 Vermont Avenue, NW Washington, DC 20420
Phone: 202-701-7628
Fax: 202-254-0473
E-mail: jeffrey.moore@va.gov
Last Updated - September 8, 2008