Reversing deficient hedgehog signaling restores deficient skeletal regeneration
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsMichael T. Longaker, Irving L. Weissman, Ruth Tevlin, Charles K. F. Chan
Life of this patent
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Abstract
Methods and compositions are provided for the therapeutic use of hedgehog agents, for enhancing bone growth and regeneration in diabetic or pre-diabetic patients, including repair following injury, osseointegration of implants, and the like. In some embodiments of the invention, the compositions are administered locally, e.g. by injection or implantation at the site of an injury.
Claims9
A method of enhancing bone repair in a human individual with diabetes, the method comprising:
- selecting for treatment a human individual with diabetes and a hedgehog signaling deficiency in the skeletal stem cell niche response to bone injury or implant;
- administering to the individual within 7 days of a bone injury or orthopedic implant a localized drug delivery device at the site of bone injury or implant, the device releasing an effective dose of Indian Hedgehog protein for a period of time of not more than one week, to overcome the hedgehog signaling deficiency in the skeletal stem cell niche;
- wherein
- injury-induced expansion and osteogenic potential of skeletal stem cells is restored at the site and bone repair is enhanced at the site of bone injury or orthopedic implant.
A method of enhancing bone repair in a human individual with diabetes, the method comprising:
- selecting for treatment a human individual with diabetes and a hedgehog signaling deficiency in the skeletal stem cell niche response to bone injury or implant;
- administering to the individual, within 7 days of a bone injury or orthopedic implant, a localized drug delivery device at the site of bone injury or implant, the device releasing an effective dose of Indian Hedgehog (IHH) protein for a period of time of not more than one week, to overcome the hedgehog signaling deficiency in the skeletal stem cell niche;
- wherein the effective dose is one or more of:
- (a) the amount of IHH necessary to accelerate bone healing by at least 25%, relative to healing in the absence of IHH;
- (b) the amount of IHH necessary to increase the presence of skeletal stem cells (SSC) by at least about 25%, relative to healing in the absence of IHH;
- (c) the amount of IHH that provides for at least 0.1 μg/kg IHH protein;
- wherein injury-induced expansion and osteogenic potential of skeletal stem cells is restored at the site and bone repair is enhanced at the site of bone injury or orthopedic implant.
Dependencies are inferred from the claim text.