Oncor Inc. licensed rights to a mutated receptor gene found in fattissue for development of a weight-loss drug, making theGaithersburg, Md., company the latest to target one of the manygenetic factors believed to be involved in obesity.
Oncor and its subsidiary, OncorPharm Inc., also of Gaithersburg,purchased rights to a mutation of the human beta-3 adrenergicreceptor gene, which was discovered by researchers at Johns HopkinsUniversity School of Medicine in Baltimore and reported in the Aug.10, 1995, New England Journal of Medicine.
OncorPharm's president and CEO, William Ryan, said the beta-3adrenergic receptor found in fat tissue of the gastrointestinal tract, isbelieved to be involved in maintaining body temperature bytriggering the process for burning calories for heat. The receptor isactivated by adrenaline.
The Johns Hopkins researchers, led by Alan Shuldiner, studiedobesity in a variety of populations, including Pima Indians inArizona, Japanese people, and Caucasians in France and Finland.The scientists found a genetically mutated beta-3 adrenergic receptorwith one amino acid out of place was common among the obesepeople studied.
The researchers said the mutation apparently results in a slowdown inmetabolism of ingested food calories, which are then stored as fat.
Ryan noted the research suggested 1 in 150 Caucasians and 1 in 70African Americans and Hispanics have two copies of the genemutation, which means they are at greater risk of becoming obese anddeveloping related complications, such as Type II diabetes and highblood pressure.
People with two copies of the mutated gene could be 30 to 50 poundsheavier than those with a normal gene, Ryan said. The effect of asingle copy of the defective gene would be more subtle.
Oncor will develop diagnostics for detecting the genetic mutation andOncorPharm will focus on drug discovery.
Ryan did not disclose financial terms of the licensing agreement withJohns Hopkins. He said OncorPharm will support continuing researchby Shuldiner's team into the function of the beta-3 adrenergicreceptor and its gene.
In addition to making cell lines expressing the defective receptor,OncorPharm will create mouse models with the normal humanadrenergic receptor gene and the mutant version in order to evaluatesmall molecule compounds.
The beta-3 adrenergic receptor's association with fat metabolism hasbeen known for years and Ryan said several pharmaceuticalcompanies are developing small molecules to stimulate the normalreceptor to burn more food calories. However, those drug candidatesmay be more effective in boosting the function of the mutatedreceptor and OncorPharm intends to approach the pharmaceuticalfirms for a possible partnership.
OncorPharm, itself, specializes in DNA code repair, which involvescorrecting the specific gene mutation that results in expression of thedefective receptor.
In their New England Journal of Medicine paper on the beta-3adrenergic receptor, the Johns Hopkins researchers stated, "Themutation may contribute to the capacity to gain weight in persons athigh risk for obesity due to other possibly additive, genetic,environmental and behavioral factors."
Oncor's stock (AMEX:ONC) closed Monday at $6, down 12 cents.
Obesity is considered a polygenic disease and the heated competitionfor developing potential drugs focuses on a number of moleculartargets.
Last week Progenitor Inc., a subsidiary of Lexington, Mass.-basedInterneuron Pharmaceuticals Inc., said it had filed an internationalpatent application for the ob receptor and its gene. The receptor,located in the brain, receives a signal from the ob gene's protein,leptin, to stop eating and to boost metabolism.
The patent application sets up a potential dispute between Progenitor,of Columbus, Ohio, and Millennium Pharmaceuticals Inc., ofCambridge, Mass., which announced last December it had discoveredthe leptin receptor and its gene.
Millennium last year also said it discovered another gene, called tub,which is believed to be involved in weight gain. Millennium, whichhas registered for an initial public offering, is researching geneticcauses of obesity under a collaboration with Roche Holdings Ltd., ofBasel, Switzerland.
The ob gene and leptin were discovered in late 1994 by researchers atNew York-based Rockefeller University, which licensed their rightsto Amgen Inc., of Thousand Oaks, Calif. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.