PARIS - The French Center for Research on Prostate Pathologies (CeRePP) has localized a gene responsible for inherited (familial) predisposition to prostate cancer on chromosome 1, at 1q42.2-43.

The gene in question, PCaP, is thought to be mutated in 50 percent of the families studied, and the linkage to the 1q42.2-43 region was found to be strongest in families where prostate cancer occurs before the age of 50. Epidemiological studies have shown that 20 percent of prostate cancer patients have an inherited predisposition in their family.

Based at the Saint-Louis Hospital, in Paris, CeRePP was set up in January 1996 specifically to identify the genetic loci predisposing to familial and sporadic prostate cancer. Early on, it entered into a gene discovery research collaboration with the Paris-based genomics company Genset, which is running its own prostate cancer research program.

CeRePP started by analyzing the genotypes of patients and their healthy relatives to associate a genetic polymorphism in a particular chromosomic region with a predisposition to cancer. The study involved the participation of hospitals in Nancy and Brest, as well as Saint-Louis Hospital, and between them they enrolled 1,000 families with two or more members suffering from prostate cancer that were willing to be genotyped. CeRePP then selected the 47 most informative families (those with three to eight prostate cancer sufferers) and performed 270,000 genotypes on them, focusing its analyses on the telomere (extremity) of the long arm of chromosome 1.

To develop its discoveries and carry them through the clinical stage, CeRePP in March established a private biotech company called UroGène SA, which is headed by the center's two senior researchers, Philippe Berthon (president and CEO) and Olivier Cussenot (chief scientific officer). Between them, Berthon (a genomics expert), Cussenot (a consultant urologist), the CeRePP itself and another senior urologist have an 80 percent shareholding in UroGène, while the remaining 20% is held by other researchers and scientists involved in the program.

Discoveries Offer Commercialization

The creation of UroGène has propelled CeRePP's researchers into the commercial arena, giving them the possibility of raising funds for financing the development and marketing of products derived from their discoveries. UroGène and CeRePP have entered into an agreement by which UroGène will own the intellectual property covering CeRePP's discoveries and pay royalties to CeRePP.

Berthon told BioWorld International “the first priority for UroGène is to conclude research and development agreements with big pharmaceutical companies.“ He said agreements currently are being negotiated with three industry leaders, two in the U.S. and one in the U.K., but he is not planning to sign agreements with all three at once because the company does not have the resources to initiate several research programs simultaneously.

“An initial contract will be signed in 1998 and a second in a year's time, and each operation will be accompanied by a search for investors,“ he explained. Research collaborations could either be exclusive or nonexclusive, depending on the type of program. “In the area of functional genomics, we have powerful tools for functional analysis, and [those] agreements would be nonexclusive.“

According to Cussenot, UroGène will develop CeRePP's gene discoveries for three purposes, of which gene therapy for prostate cancer is only one. In addition, it will provide the medical profession with new diagnostic tools for designating the individuals at risk in families identified as being prone to prostate cancer, and will develop more conventional therapeutic and pharmacological devices for treating the disease.

BPH Another Target

In addition to studying prostate cancer in all its forms, CeRePP also is conducting research into other urological conditions that have significant genetic etiological components, such as benign prostatic hyperplasia (BPH). “Our work will continue to be focused on genes associated with prostate cancer in the first instance, but later we will extend it to other organs, such as the bladder,“ said Berthon.

UroGène possesses a number of proprietary developmental and etiological tools developed by CeRePP. These include:

* UroSignal, which mimics physiological reactions to insult at different developmentally or pathologically relevant stages, enabling UroGène to establish and modify the cell lines specific to developmental stages.

* UroAtlas, which is designed to fill in an array of related molecules around a gene candidate, and which UroGène is using to develop the array technology specific to pathophysiology encountered in the prostate, bladder and urinary tract.

* UroTraces, which catalogues the expression of urologically focused sets of proteins to circumvent complicated test protocols. By indicating simple, relevant molecular criteria, it facilitates the characterization of the proteins associated with healthy and diseased tissue.

UroGène claims these tools will enable it to reduce drug discovery time substantially because they target choices on the basis of reliable, quantitative criteria in cell lines as well as in microdissected tissues from patients. It intends not only to establish new molecular criteria, but to make critical location and kinetics criteria available to customers and partners for preclinical studies.

Prostate cancer results in 8,000 fatalities each year in France. There are estimated to be more than 200,000 sufferers in the country, with some 14,000 new cases diagnosed each year. *