Clozapine is an antipsychotic drug that is used to treat psychotic conditions such as schizophrenia.  It is a very effective drug and is used to treat schizophrenia that is resistant to treatment with other drugs.   It also reduces the risk of suicidal behaviour in patients with schizophrenia.  Were it not for a major side effect it would be first line treatment:  it causes potentially lethal agranulocytosis in about 1% of patients and is relegated to third-line use.   Agranulocytosis (a lack of granulocytes) is an acute condition involving a severe and dangerous leukopenia (reduction in the number of white blood cells) in the body.  It can cause the body to become susceptible to infection and early symptoms include sudden fever, rigors and sore throat. Ultimately, it can lead to the rapid and progressive infection of any organ (e.g. pneumonia, urinary tract infection).

The molecular triggers trying underling clozapine-induced agranulocytois are not known and we will use biochemical and genetic screens to identify putative molecular mechanisms underlying this serious side-effect.