PARIS ¿ The Paris-based genomics company Genset has created a physiological genomics department at its La Jolla, Calif.-based subsidiary, Genset Corp., to expand and develop its gene discovery research into obesity and metabolic disorders. This is by far the most advanced of the company¿s in-house gene discovery programs, according to managing director Marc Vasseur, although it started in 1997 as a collaboration with France¿s National Institute for Health and Medical Research (Institut National de la Santi et de la Recherche Midicale, or INSERM).

Genset and INSERM set up a joint molecular physiology laboratory in Rennes, in northwestern France, after signing a cooperation agreement in March 1997, and the following August they filed their first joint patent application, which was for a gene coding for the lipolysis-stimulated receptor (LSR). Genset¿s collaboration with INSERM was abruptly terminated last summer, however, in the wake of allegations about the integrity of the laboratory¿s director and the validity of the research being carried out there. Since then, Genset has continued the research on its own.

The program is aimed at identifying the metabolic mechanisms behind the development of obesity and its complications. It focused initially on the mechanisms that control the distribution of alimentary lipids absorbed by the intestine, using the methods of molecular physiology and genetics. For Genset, the discovery of the gene coding for the LSR, a receptor that limits the distribution of alimentary lipids to the liver, was a ¿very promising¿ first step, and these initial results are to be published in the upcoming issue of the Journal of Biological Chemistry.

On the strength of this early success, Genset has decided to step up its obesity research program by creating this new department specialized in physiological genomics. Headed by Bernard Bihain, previously with INSERM, it will be able to exploit collections of clinical samples taken from hundreds of obesity sufferers with very specific phenotypical characteristics, and compare them with control samples from non-obese people.

Genset has identified a set of polymorphisms at the level of the LSR gene and is now undertaking large-scale association studies to discover and characterize other genes that could be associated with the mechanisms leading to obesity.

Among other things, Genset has identified a new mechanism controlling the elimination of alimentary lipids that is involved in the development of obesity, and has filed four patent applications covering the genes and polymorphisms associated with it. Vasseur claims that this ¿solid portfolio of patents¿ gives the company ¿exceptional commercial opportunities¿ in the world obesity market, said to be worth an estimated $10 billion to $15 billion a year. Genset intends to negotiate collaboration deals with pharmaceutical companies, and license out its obesity-related gene discoveries for drug discovery and development. n