HAMBURG, Germany - Lion Bioscience AG, an integrated genomics company, and Infogen Medizinische Genetik GmbH, a population genetics company, entered a collaboration to identify new genes in the area of cardiovascular diseases. The partners intend to provide insights into disease mechanisms and to find new therapeutic targets.

For Lion, of Heidelberg, the collaboration is a logical step. Founded in March 1997, the company has grown from a dozen staffers to more than 80. Its focus on sequencing combined with bioinformatics has led to a portfolio of techniques and services to make the most of sequence and genomics data. It has attracted an impressive list of customers, ranging from pharmaceutical giants such as Bayer AG, of Leverkusen, and Hoechst AG, of Frankfurt, to small and medium-sized companies from the chemical to agrobiotechnology sectors. (See BioWorld International, April 8, 1998, p. 1.)

“In the long run, just providing sequencing data is not an ideal growth strategy,“ Claus Kremoser, director of strategy and business development, told BioWorld International. “However, there is a growing market for additional information, i.e., identification and validation of target genes and lead molecules.“

Therefore, Lion not only provides automated, high-throughput genomics technologies, but has developed tools to provide in-depth analysis of genes. Bioinformatics software such as the company's bioSCOUT can even analyze gene sequences automatically. It gathers database information on similar and homologous sequences and generates two- and three-dimensional structures.

Discovery has been established as a third business activity. “Gene discovery is a perfect complement to our already existing core competencies,“ said Friedrich von Bohlen, founder and CEO of Lion. “We want to become a leading provider of functionally validated target genes, and therefore we will start self-funded research projects to explore promising genes. To achieve this aim, Infogen is a very valuable partner.“

Berlin-based Infogen was founded in 1996 by Herbert Schuster, a physician and medical geneticist at the Max Delbruck Center for Molecular Medicine, in Berlin. The start-up employs 10 scientists from different disciplines. Schuster developed a genetic test for familial hypercholesterolemia two years ago. (See BioWorld International, Oct. 9, 1996, p. 1.)

“As a physician with strong interest in molecular biology, I realized that there is a huge potential in risk assessment of families where individual members show a high incidence towards common cardiovascular diseases,“ Schuster said. “Patients with high levels of blood lipids or hypertension or relatives of them are invited to participate in a family-based risk assessment and, if necessary, in a phenotype-genotype analysis.“

The identification of genetic markers which correlate with certain disorders allows the physician to estimate the individual's risk. “Therefore,“ Schuster said, “the primary benefit for the patients lies in this family-based risk assessment.“

So far, Infogen has gathered pedigrees with up to 80 members and collected samples from more than 5,000 individuals. “Moreover, the additional value of our 'genetic fieldworking' approach is given through using the collection of samples for the mapping and identification of novel genes, which are causative agents of the cardiovascular phenotypes we observe,“ Schuster continued. “Infogen and Lion will take this gene hunt forward, which will eventually lead to new diagnostic and therapeutic approaches for the diseases.

Highly Selected Phenotypes Targeted

“In contrast to other gene hunting projects which rely on screening entire populations, we are focussing on voluntary patients which have a defined phenotype out of selected sets of diseases,“ Schuster added. Individuals under investigation are well informed and have given their written consent. “Therefore, we are not in danger to run into any legal or ethical problems,“ Schuster said. “Already we know some genes which are responsible for certain cardiovascular diseases in some very rare and small families. However, to understand the broad spectrum of cardiovascular diseases in the broad population, one has to know the modulating genes to understand the mode of action and the regulatory mechanism.“

Ralf Tolle, director of molecular medicine for Lion, said the alliance will concentrate on highly selected and well-characterized phenotypes.

“We want to identify target genes not only for diagnostic purposes but for drug development as well,“ he said. “Moreover, by mapping and analysis of relevant polymorphisms, our alliance will be able to genetically differentiate drug responders from nonresponders. Because the administered drug regimen is well recorded, we can use this extremely valuable collection of patient samples and their corresponding pathophysiological data for a true pharmacogenetic screen.“

For Schuster, the partnership is a “win-win situation.“ Infogen is a company embedded in an academic research environment, and provides expertise in phenotyping, patient stratification and medical informatics, he said, while Lion is a strong industrial partner with very valuable genotyping and sequencing capacity and “perfect bioinformatic skills.“

Financial details of the collaboration were not disclosed, but von Bohlen said Lion would be responsible for commercializing the results. The alliance also will develop software tools for the analysis of family trees and genotype-phenotype interactions and add these tools to the bioSCOUT bioinformatics system. Information relevant for new drug development and the assessment of drug responsiveness will be shared with partners. *

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