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DeCode Genetics Pursues Respiratory Drug Targets in $24M, 5-Year NIH NIAID Study

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In a $24 million study that may yield valuable drug targets and a vaccine-response screen, the US National Institute of Allergy and Infectious Diseases will support research by DeCode Genetics, University of New Mexico scientists, and the National Center for Genome Resources into respiratory pathogen and smallpox vaccine responses.

The three organizations involved in the study will link genes responsible for susceptibility and resistance to “fairly common” infectious diseases, as well as genes that confer rare but serious adverse events to smallpox vaccine, said Rick Lyons, director of the University of New Mexico Health Sciences Center Infectious Disease and Inflammation Center.

Once the study is complete, DeCode will have access to its gene expression and proteomic data, which include information on susceptibility to influenza, tuberculosis, and infection-causing encapsulated bacteria, which may “include haemophilus, streptococcus — things like that,” said Lyons.

DeCode is “very keen” to use its “medicinal chemistry capabilities” to take these discoveries and validate them as targets and put them into screening, said Stephen Kingsmore, president of NCGR.

In a press conference last week announcing the study, DeCode CEO Kari Stefansson was “very clear” this approach is how the company hopes to offset its R&D cost, said Kingsmore. The company has “considerable intent to actually develop drugs or vaccines, or improve vaccines based on what they find,” he added.

According to Nasrin Nabavi, program officer for the NIAID Division of Allergy, Immunology, and Transplantation, DeCode will make data public at particular periods during the study, although no dates have been set, she added.

The Institute of Allergy and Infectious Disease will fund DeCode through a $24 million cost-reinvestment contract, while the company will subcontract work to the UNM HSC and the NCGR, said Nabavi.

DeCode did not return numerous requests for comment for this article.

Through its database, DeCode had identified a “large number” of families, “sometimes hundreds of families,” relevant to the study, said Kingsmore. The database includes genetic information on about 110,000 Icelanders — more than half of the island’s population — and a wealth of medical information from the country’s public health-system records.

University of New Mexico HSC researchers will evaluate the candidates with proteomic and gene expression methods, said Lyons. “It’s a five-year contract, and it’s pretty complex. Hopefully we will get data out for at least one of the pathogens in the first year or year-and-a-half,” he said. The individual pathogen tests have not been prioritized yet, but “there is a lot of interest in looking at” tuberculosis and influenza, he added.

According to a NIAID spokesperson, the agency obligated more than $200 million for smallpox research and development in fiscal year 2004, most of it in support of the smallpox vaccine MVA. “Several million" were also provided in support of smallpox antivirals, she said. The agency is not yet able to break out funding for specific disease areas for fiscal year 2004, she added.

In 2002, there were 15,075 tuberculosis cases in the United States, according to the US Centers for Disease Control and Prevention.

The HSC will be looking at cells important to immune response, “like dentritic cells and monocytes,” said Lyons. After DeCode finds sensitive or resistant individuals in their genetic mapping studies, the HSC will link cellular pathogen responses to protein and gene expression patterns. DeCode hopes to then identify drug targets, while the vaccine response may be useful for a screen for people “at risk” for an adverse response, said Lyons.

“If you know the gene or polymorphism — or whatever you’re looking for — you could develop a very rapid high-throughput blood screen for that. That would not be difficult,” Lyons said. But there is no definite plan to produce a screen related to the vaccinations, he said.

The NCGR, a nonprofit bioinformatics institute, will integrate study data into an Immune Response Database available on the Internet. DeCode will generate the genetic and linkage data, and NCGR will “provide that through an Internet site to NIAID,” said Kingsmore, the group’s president.

“Pretty much everybody in the biotech industry is looking for assured revenue of this type — and very glad to be involved. Anytime you can bring a five-year definite revenue stream, people are keen to do it. You can expect to get a bunch more of these in the future,” said Kingsmore.

DeCode has enough information to analyze the genetics of as many as 50 different ailments, said CEO Kari Stefansson in the September issue of Technology Review magazine.

— CW

 

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