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'Connectivity Map' uncovers links between disease and drugs

1 October 2006
Appeared in BioNews 378

US scientists have developed a new method of matching potentially effective drugs with diseases in a publicly accessible web based program known as the 'Connectivity Map'. The method relies on describing both drugs and diseases in a 'common language' of genomic signatures so that the two can be matched. So far the method has uncovered a possible new treatment for acute lymphoblastic leukaemia - a type of cancer usually resistant to steroid treatment. The potential new treatment utilises an immunosuppressant drug known as 'rapamycin' that already has American Food and Drug Administration (FDA) approval for use. The team are also investigating potential drugs that appear to act in roughly the opposite way to certain genes found in brains of patients suffering from Alzheimer's disease.

The team, based at the Broad Institute in Massachusetts - a collaboration between the Massachusetts Institute of Technology (MIT) and Harvard University - began by using technology known as microarrays to uncover genetic changes in particular disease cells, and how they changed when exposed to various drugs. The results were entered into the prototype connectivity map. Todd Golub, director of the cancer programme at the Broad Institute said that 'the connectivity map works much like a Google search to discover connections among drugs and diseases. These connections are notoriously difficult to find in part because drugs and diseases are characterised in completely different scientific languages'. For the pilot project the scientists measured the genomic signatures of more than 160 drugs and other biologically active compounds. There are more than 1400 drugs currently approved by the FDA.

The new tool was unveiled in three journal papers published in Science and Cancer Cell. Lead author of the Science paper, Justin Lamb, also of the Broad Institute Cancer Programme commented: 'This is a powerful discovery tool for the scientific community. By analysing just a small fraction of available drugs, we have already confirmed several biological connections between drugs and human disease, and made entirely new ones too'. One of these new discoveries shows that an existing drug called gedunin, derived from plant extracts, which was previously not well understood, may be effective in treating prostate cancer. The team hope that the pilot database can now be expanded to include all approved drugs, allowing new uses to be found for existing drugs and speeding up development of new treatments. The database could also be used to store information about gene activity in particular diseases which may reveal familiar genetic signatures applicable in other illnesses that have not been so well studied.

SOURCES & REFERENCES
Genetic database to fight disease
Nature |  28 September 2006
Genetic 'roadmap' charts links between drugs and human disease
EurekaAlert |  28 September 2006
Genetic 'search engine' will let doctors match drugs to diseases
The Independent |  29 September 2006
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