Description of Invention:
This application describes and claims novel pharmocoactive compounds which belong to the class of compounds known as polyketide macrolides. These compounds have been isolated from M. ulcerans, the causative agent of buruli ulcers. Early work with these compounds suggests that the principle compound, mycolactone, or mixtures of mycolactone with other isolated polyketide macrolides or other agents may be useful in treating cancer or suppressing an inflammatory response.
In addition to the novel polyketide macrolide compounds the application also describes compositions derived from a non-virulent strain of M. ulcerans. These compositions may be useful in inducing an immune response (vaccines) which could be useful in providing subjects with resistance to the development of buruli ulcers. Antibodies against mycolactone are being developed. These antibodies could be used for diagnostic purposes.
Inventors:
Pamela L. Small and Kathleen M. George (NIAID)
Patent Status:
DHHS Reference No. E-199-1999/0 --
U.S. Patent 6,680,055 issued 20 Jan 2004
Relevant Publication: Some early publications which describe this work are:
KM George et al. Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science 1999 Feb 5;283(5403):854-857. (PubMed abs)
KM George et al. Partial purification and characterization of biological effects of a lipid toxin produced by Mycobacterium ulcerans. Infect Immun. 1998 Feb;66(2):587-593. (PubMed abs)
More recently, novel mycolactones have been isolated and characterized from:
Australian isolates of M. ulcerans [TC Judd et al. Structure determination of mycolactone C via total synthesis. Organic Lett. 2004 Dec 23;6:4901-4904. (PubMed abs)], as well as
the frog pathogen M. liflandii [A Mve-Obiang et al. A newly discovered mycobacterial pathogen isolated from laboratory colonies of Xenopus species with lethal infections produces a novel form of mycolactone, the Mycobacterium ulcerans macrolide toxin. Infect Immun. 2005 Jun;73(6):3307-3312. (PubMed abs)].
Portfolios: Internal Medicine Cancer
Cancer -Therapeutics-Vaccines Cancer -Therapeutics-Other Internal Medicine-Therapeutics-Anti-Inflammatory (including Autoimmune) Cancer -Therapeutics Internal Medicine-Therapeutics
For Additional Information Please Contact: John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-5236
Email: stansbej@mail.nih.gov
Fax: (301) 402-0220
