BACKGROUND:  As one of the key regulators of development in varied organisms from Drosophila to humans, the hedgehog pathway is an important component of embryonic growth and stem cell expansion. The pathway was originally implicated in the embryogenesis of fruit flies, contributing to the body segmentation of a developing Drosophila embryo. Sonic hedgehog (Shh), the mammalian homolog of the ligand, plays a role in both early and late development processes in vertebrates. Recent findings suggest that abnormal activation of the hedgehog pathway is implicated in pathologies such as cancer and skeletal diseases, conveying its therapeutic relevance. Efforts by pharmaceutical and biotech industries are being made to find small molecule antagonists that directly antagonize hedgehog signaling. Novel strategies for inhibition of dysregulated hedgehog signaling may have benefits in the better management and treatment of various human cancers and other illnesses.

INNOVATION:  Researchers at the David Geffen School of Medicine at UCLA have identified a novel interaction between hedgehog signaling and the activation of a nuclear hormone receptor. Activating this nuclear hormone receptor has been found to inhibit hedgehog signaling, which creates a new strategy for interfering with dysregulated hedgehog pathway activity. Pilot studies were conducted to test the strategy, where cells were treated with Shh in the presence or absence of activators of the nuclear hormone receptor. Results showed a complete inhibition of the biological activity of Shh upon co-activation of the nuclear hormone receptor.

POTENTIAL APPLICATIONS 

• Parenteral or oral therapeutics aimed at cancers of brain, lungs, and the gastrointestinal tracts.
• Topical treatment of basal cell carcinoma.
• Pharmaceuticals for neurodegenerative disorders, such as Parkinson's.

ADVANTAGES

• The strategy provides a novel way to inhibit the hedgehog signaling pathway.
• The invention presents new alternatives to invasive cancer therapies like radiation and chemotherapy.

DEVELOPMENT-TO-DATE:  Invention has been developed conceptually and has been tested in vitro.

Reference: UCLA Case No. 2006-739