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Novel Inhibitors of Bone Morphogenetic Proteins

Bone Morphogenetic Proteins (BMPs) are signaling molecules that are central in a variety of biological processes, but were first recognized for their role in inducing bone and cartilage development. Abnormal BMP signaling has been implicated in the pathogenesis of a class of joint disorders known as spondyloarthropathies which includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and arthritis associated with inflammatory bowel disease. Therefore, inhibitors and modulators of BMP signaling may be useful in managing these disorders. Moreover, the BMPs and their antagonists have now been implicated in myriad cell and tissue differentiation and fate specification processes, extending their utility far beyond orthopedic and rheumatologic applications. Scientists at the Food and Drug Administration, National Institutes of Health and Katholieke Universiteit Leuven have discovered a novel inhibitor of BMPs called Secreted Modular Calcium Binding protein (SMOC) which is unrelated to known BMP inhibitors.

This technology relates to a method for treating disorders including joint disorders by administering a SMOC polypeptide to induce intracellular mitogen activated protein (MAP) kinase activity to effect a reduction of BMP signaling activity in the cells of a patient. It also encompasses methods to manipulate differentiation processes regulated by BMPs. One prominent example is the specification of neural, as opposed to epithelial, cell fate.

Potential Commercial Applications:

  • Treatment of joint diseases
  • Manipulation of tissue fate specification in vitro, alone or in combination with other materials, in production of therapeutic cells and tissues

Competitive Advantages:

  • Ability to interrupt BMP signaling by a novel mechanism
  • Predictable synergy with other BMP antagonists
  • No indication of being immunosuppressive
  • In some instances SMOC is associated with extracellular matrix molecules, allowing for spatially restricted BMP antagonism not possible with diffusible factors such as noggin


Inventors:
Malcolm Moos
Frank Luyten

Intellectual Property:
PCT Application No. PCT/US2009/052373
US Application No. 13/057,545

Publications:
None related to this invention.

Licensing Contact:
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
10903 New Hampshire Ave.
Building WO1, Rm 4214
Silver Spring, MD 20993
Email: FDAInventionlicensing@fda.hhs.gov
Phone: 240-402-4561

OTT Reference No: E-338-2005/0
Updated: August 9, 2015