NIH Invention Disclosures, Oct. 29, 1996
Invention disclosures forwarded for publication in the Federal Register by NIH on October 29, 1996
A Method For Imaging Nicotinic Acetylcholinergic Receptors In The Brain Using Radiolabeled Pyridyl 7-Azabicycloheptanes
Description of Invention:
The current invention embodies the use of radiolabeled analogs of epibatidine to noninvasively image and quantify levels of nicotinic acetylcholine receptors in a living mammalian brain, using Positron Emission Tomography or other nuclear medicine methods. As nicotinic acetylcholine receptors have been implicated in various neuropathological and physiological disorders, including Alzheimer's disease, the invention may represent a powerful new method for the noninvasive diagnosis of Alzheimer's disease and other disorders. In addition, the method embodied in the invention may prove valuable for use in monitoring the progression of various disorders and in determining the efficacy of drug therapy protocols used in the treatment of these disorders.
Inventors:
ED London, AS Kimes, A Horti, RF Dannals, M Kassiou (NIDA)
Patent Status:
U.S. Patent Application No. 08/642,636 filed 06 May 96
Portfolio:
Central Nervous System - Diagnostics, in vivo
For additional information, please contact:
Stephen Finley, Ph.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext. 215
Fax: 301/402-0220
Identification of an Allelic Ser857-Asn857 Variation of the Human Delayed Rectifier Potassium Channel DRK1 (KCNB1 locus)
Description of Invention:
The DRK1 potassium channel is voltage sensitive such that as phosphorylation of the protein is increased the current is reduced, thereby increasing the cell's excitability. The amino- and carboxyl-terminal regions of DRK1 are located in the cytoplasm. A new, but naturally occurring substitution of the human delayed rectifier potassium channel DRK1 (KCNB1 locus) was mapped to chromosome 20q13.2. The nonconservative substitution occurs at position 857 in the carboxy terminal region of the protein. Transmembrane sequences of the rat and human DRK1 have been shown elsewhere to be identical, but have different pharmacological and conductance differences. The substitution of cytoplasmic serine to asparagine may effectively remove a possible phosphorylation site which could result in increased excitability of the cell or effect the function of the protein by altering the conformation, thereby accounting for the pharmacological and conductance changes. The DRK1 was mapped to the same locus as the dominantly inherited EEG trait difference, a low voltage alpha trait difference (20q13.3-13.3), but no correlation could be found between the substitution and the low voltage alpha trait.
Potential Areas of Application:
Association analysis of neurological traits mapped to chromosome 20q13.3
Investigation of the function of conserved carboxy terminal regions of Shab-type potassium channels
Main Advantages of Invention:
Well-characterized method for genotyping variant for large-scale screening
Multiple populations already characterized for frequency of variant
Stage of Development:
Genetic variant described
Further Development Required:
No further development required for patient/population screening
Inventors:
D Goldman, AW Bergen, CM Mazzanti, S Michelini (NIAAA)
Recent Relevant Publication:
Mazzanti CM, Bergen A, Enoch M-A, Michelini S, and Goldman D: "Identification of a Ser857-Asn857 substitution in DRK1 (KCNB1), population frequencies and lack of association to the low voltage alpha EEG trait," Human Genetics 98: 134-137, 1996.
Patent Status:
Serial No. 60/020,348 filed 24 Jun 96
Portfolios:
Central Nervous System - Therapeutics, psychotherapeutics
Central Nervous System - Diagnostics
Central Nervous System - Research Materials
For additional information, please contact:
Stephen Finley, Ph.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext. 215
Fax: 301/402-0220