Decode genetics announced that it has isolated two new genes as part of its alliance with Merck & Co, Inc. to develop drugs for the treatment of obesity. Following the gene discovery announced in September, Decode scientists have discovered common versions of two additional genes that significantly predispose individuals to obesity. The companies are now analyzing the genes and the biological pathways they delineate to select optimal targets for the development of new drugs.
The genes were identified through population- and genome-wide linkage scans and association analyses of at-risk haplotypes utilizing genetic and clinical data from the 17,000 participants in Decode's obesity programme in Iceland. The discovery of one of the genes resulted from the analysis of high-density SNP and microsatellite genotyping of more than 900 men with high body-mass index (BMI) and several hundred non-obese relatives and random controls. The at-risk haplotypes, or versions of the gene linked to obesity, were found in more than one in four individuals with high BMI, and were three times more common in these individuals than in controls. This gene, which the companies believe is involved in regulating how the body stores and uses energy, implicates a novel pathway in human obesity.
The at-risk versions of the second gene, which was identified through analysis of 125 families that include multiple women with a high percentage of body fat (PBF), were carried by 22per cent of those with high PBF. These haplotypes increase the risk of obesity by a factor of five. This gene appears to contribute to obesity through the regulation of appetite.
"These findings demonstrate yet again the power of our capabilities in human genetics for discovering major new targets and pathways involved in the most complex medical conditions. We have identified common alleles of genes that contribute significantly to both of the principal processes involved in obesity - basic energy metabolism on the one hand and the regulation of appetite on the other," said Kari Stefansson, CEO of Decode. "With our partners at Merck we are bringing together these findings with extensive work in mouse genetics and biology, giving us a strong starting point for beginning the development of novel drugs for the treatment of obesity."
The prevalence of obesity continues to increase throughout the developed and developing world. Obesity, through its co-morbidities such as diabetes, lipid disorders, and hypertension, contributes greatly to human disease. Together, Decode and Merck are working to identify novel mechanisms to be targeted by drugs for the treatment of obesity.
Decode is turning research on the genetic causes of common diseases into a growing pipeline of products and services - in pharmaceuticals, gene and drug discovery, DNA-based diagnostics, pharmacogenomics, bioinformatics, and clinical trials. Decode's pharmaceuticals group, based in Chicago, and Decode's biostructures group, based in Seattle, conduct downstream development work on targets derived from Decode's proprietary research in human genetics as well as contract service work for pharmaceutical and biotechnology companies.