Novel Roles of a DNA Repair Protein, DNA-PKcs, in Obesity, Neurological Function, and Aging


The catalytic subunit of the DNA-dependent protein kinase complex (DNA-PKcs) has been shown to be important in DNA repair and VDJ recombination in lymphocytes. The inventors have discovered that DNA-PKcs also plays novel, important roles in energy regulation and neurological function. The inventors observed that mature DNA-PKcs-deficient mice (also known as SCID mice) have a lower proportion of fat, resist obesity, and have significantly greater physical endurance than wild-type control mice, particularly with increasing age. The inventors also observed that DNA-PKcs-deficient mice have better memory and less anxiety. One potential explanation for this is that they express higher levels of brain-derived neurotrophic factor (BDNF), which is associated with neurogenesis, memory formation and suppression of anxiety and depression. Moreover, DNA-PKcs-deficient cells produce less oxidative stress. Thus, inhibition of DNA-PKcs may have unexpected utility in the treatment of a wide range of diseases and conditions.

The invention discloses methods of inhibiting DNA-PKcs activity to decrease adiposity, improve physical endurance and increase insulin sensitivity and the number of mitochondria. Also claimed are methods directed to improved neurological function, such as methods for protection from neurodegenerative disease, improving memory and learning ability, and for reducing depression and anxiety. Additionally, the invention discloses methods for reducing inflammation and for treating heart disease.

Potential Commercial Applications: Competitive Advantages:
  • Development of therapeutics targeting obesity, insulin-resistant diabetes, and age-related loss of physical endurance.
  • Development of therapeutics to treat neurological disorders such as depression and memory loss.
 


Development Stage:
Early stage

Inventors:

Jay Chung (NHLBI)  ➽ more inventions...


Intellectual Property:
PCT Pat: - issued -
US Application No. 60/958,714 filed on 2007-07-06
US Application No. 12/667,840 filed on 2010-02-01

Publications:
In preparation

Collaboration Opportunity:

The National Heart Lung and Blood Institute, Laboratory of Biochemical Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize DNA-PKcs inhibitors for treatment or prevention of metabolic and degenerative diseases. Please contact Jay Chung (chungj@nhlbi.nih.gov) for more information.


Licensing Contact:
Michael Shmilovich, J.D.
Email: shmilovm@mail.nih.gov
Phone: 301-435-5019

OTT Reference No: E-068-2007-0
Updated: Sep 2, 2009