NEW YORK (GenomeWeb News) – Duke University's Center for Human Genome Variation and the International Serious Adverse Events Consortium plan to collaborate on research into the role of rare genetic variants in a drug-induced adverse event involving an antipsychotic drug called clozapine, SAEC announced today.
Through the collaboration, researchers hope to find rare genetic variants that can be used to predict an individual's risk of a condition called clozapine-induced agranulocytosis, or CIA, which leads to an inability for a person's bone marrow to produce enough white blood cells, decreasing their immune response.
The team plans to expand on published data on associations between the chromosome 6 HLA region and CIA using a whole-genome sequencing approach. They will reportedly use CIA cohort materials and data provided to SAEC by Clinical Data division PGx Health.
Clozapine is often used to treat schizophrenia patients, particularly those who don't respond to other drug treatments. But because it's estimated that the antipsychotic causes CIA in around two percent of individuals taking it, the drug is available through a Food and Drug Administration sanctioned surveillance system called the Clozapine Patient Management System. As part of this program, individuals taking clozapine have their white cells checked weekly before getting their supply of the drug.
"For many patients clozapine is the most effective drug available, but its use is constrained by the possibility of this serious adverse event requiring intrusive monitoring programs," project leader David Goldstein, director of Duke's Center for Human Genome Variation, said in a statement. "We hope that understanding the genetics of CIA will not only reduce its occurrence, but also allow wider use of clozapine."
Duke psychiatry researcher Anna Need is co-managing the collaboration between Duke University and SAEC, an international, non-profit research consortium spawned by the global pharmaceutical industry.
"By researching the genetics of drug-induced CIA, we hope to further our understanding into the genetics of immunologically mediated adverse drug responses," SAEC Chairman Arthur Holden said in a statement. "Our collaboration with Duke University's Center for Human Genome Variation represents our first pilot to use whole-genome sequencing technology to better understand the role of rare genetic variation in such event."