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mTOR Inhibition for the Prevention of Epithelial Stem Cell Loss and Mucositis

Posted Mar 11 2013 8:00pm

Description of Invention:
The integrity of the epidermis and mucosal epithelia is highly dependent on self-renewing stem cells and, therefore, is vulnerable to physical and chemical damage from common cancer treatments, such as radiation or chemotherapy. Consequently, many cancer patients undergoing these treatments develop mucositis, a debilitating condition involving painful and deep mucosal ulcerations. Since current prevention and treatment options for mucositis are limited, providing only minor relief and no protection to stem cells, novel therapies are needed.

The NIH inventors have recently discovered that the mammalian target of rapamycin (mTOR) mediates stem cells exhaustion in the skin and leads to progressive hair loss. More importantly, they have shown that mTOR inhibition reduces oxidative stress in the epithelial stem cells and mTOR inhibitors can be used to increase the re-populative capacity of tissue resident stem cells to maintain tissue homeostasis after injury or stress. Therefore, this technology could be used to prevent epithelial stem cell loss and provide relief from radiation-induced mucositis. Likewise, it could be used to prevent mucositis and hair loss in patients undergoing chemotherapy and stem cell transplantation. For optimal delivery and effectiveness, rapamycin or other mTOR inhibitor could be administered in the form of a mouthwash or gel product to patients prior to receiving radiation (or other) treatments.

Applications:
Prevention and treatment of epithelial stem cell loss and mucositis.

Advantages:
  • Reduces the oxidative stress in epithelial stem cells and can increase their repopulative capacity.
  • Preserves the integrity of the oral mucosa and protects from radiation-induced stem cell loss and mucositis.


Development Status:
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:
J Silvio Gutkind (NIDCR)
Vyomesh Patel (NIDCR)
Alfredo A Molinolo (NIDCR)
Ramiro Iglesias-Bartolome (NIDCR)
Ana P Cotrim (NIDCR)
James B Mitchell (NCI)


Patent Status:
HHS, Reference No. E-257-2012/0
US, Application No. 61/696,861 filed 05 Sep 2012


Related Technologies:
US, Application No. 13/376,984 filed 08 Dec 2011, Reference No. E-300-2008/0
US, Application No. 61/186,582 filed 12 Jun 2009, Reference No. E-300-2008/0


Relevant Publication:
  1. Iglesias-Bartolome R, et al. [ PMID 22958932 ]



For Licensing Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220


Ref No: 2543

Updated: 03/2013

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