Vertex Pharmaceuticals Inc. announced Wednesday that it hasacquired exclusive worldwide rights from the Children'sHospital Oakland (CHO) to develop, manufacture and marketcompounds to treat hemoglobin disorders such as sickle cellanemia and beta thalassemia.

Patients suffering from these genetic disorders have adefective or incomplete adult form of hemoglobin. But clinicalstudies have demonstrated that it's possible to ameliorate theseconditions by inducing these patients to start producing fetalhemoglobin -- the gene for which is normally turned off afterinfancy -- by intravenous administration of arginine butyrate,a naturally occurring fatty acid.

Vertex has licensed arginine butyrate (and related organiccompounds) from CHO, which holds the U.S. use patents.

Researchers from the Children's Hospital Oakland ResearchInstitute in California and their collaborators published thepreliminary clinical results in The New England Journal ofMedicine in January.

The compounds are believed to act as transcriptional activatorsto reactivate the fetal hemoglobin gene, which in adults iseither turned off or is expressing at a level equal to less than 1percent of adult hemoglobin, explained Joshua Boger, Vertex'spresident and chief executive officer.

Although the exact molecular mechanism by which argininebutyrate acts as a transcriptional activator is not yet known,the functional definition is enough. "When we give argininebutyrate (to patients), hemoglobin production goes up," Bogertold BioWorld.

Vertex (NASDAQ:VRTX) plans to take the compound throughclinical testing. "The agreement provides an opportunity forVertex to develop products with demonstrated clinical promisein an area where there is an important medical need," Bogersaid.

However, the Cambridge, Mass., company also intends toexplore the molecular mechanisms by which the compoundswork. According to Boger, "The precise steps by which argininebutyrate (which Vertex has designated as VX105) and therelated compound for oral administration (which Vertex callsVX366) work to activate transcription are important tounderstand" before creating a "second-generation" productusing Vertex's expertise in structure-based rational drugdesign. "We don't know what characteristics to improve yet," hesaid.

Still, Boger said that his company has the advantage of beingable to apply its drug-design methodology to a targetcompound that's already been shown to work in humans andthat appears to be safe. "Understanding that concept -- tofollow the leads of compounds that work -- may be the key tobeing able to design drugs to modulate or control thetranscription of other genes in other diseases," Boger explained.

-- Jennifer Van Brunt Senior Editor

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