Inhibition of Smad3 to Prevent Fibrosis and Improve Wound Healing
Description of Invention:
Millions of dollars are spent each year to heal chronic non-healing wounds and in the treatment of severe burn patients. The NIH announces a new technology that may lead to improved approaches to treatment of burn patients and the reduction of scarring and more rapid closure of both acute (surgical) and chronic wounds (e.g., diabetic, decubitus, and venus statis ulcers).
Smad2 and Smad3 are highly homologous cytoplasmic proteins which function to transduce signals from Transforming Growth Factor-beta (TGF-beta) and activin receptors to promoters of target genes found in the nucleus. This new technology indicates that interference with specific signaling pathways downstream of TGF-beta may be more selective and have a better outcome than approaches aimed at blocking all effects of this pleiotropic cytokine.
Specifically, it is proposed that elimination or inhibition of Smad3 may interfere with fibrogenic mechanisms and reduce the accumulation of scar tissue associated with high dose radiation and wound healing, while increasing the rate of re-epithelialization of wounds.
Although this technology is still in an early stage, our researchers have obtained solid evidence of the involvement of Smad3 in these processes by use of a Smad3 null mouse model which they have developed. Based on these results, it is believed that antisense Smad3 or small molecule inhibitors of Smad3 will have clinical applications in wound healing, in improving growth and reducing unwanted fibrosis of autologous skin grafts for treatment of burn patients, and in treatment of radiation fibrosis and other fibrotic diseases associated with chronic inflammation. In addition, the discovery of inhibitors to Smad3 signaling may lead to radiation dose escalation and accelerated tumor cell death while reducing the side effects associated with radiation therapy.
Inventors:
Anita B. Roberts et al. (NCI)
Patent Status:
DHHS Reference No. E-070-2000/0 Licensing Status: This technology is no longer available for licensing.
For Additional Information Please Contact: Catherine A. Wendelken JD, MIP
Office of Technology Transfer
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Phone: (301)435-5282
Email: wendelkenc@mail.nih.gov
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