schizophrenia

Schizophrenia is a chronic progressive highly disabling and distressing disease. Patients suffer from a serious disorder affecting the ways they perceive the world around them that profoundly decreases their ability to function normally. Specifically, schizophrenia patients have difficulty separating real from imaginary experiences, suffer from inappropriate emotions and behaviors and have cognitive impairment. As a result, schizophrenia patients often withdraw from society and are unable to support themselves.

The prevalence of schizophrenia is estimated at about 1% of the population worldwide. Estimates of the costs to society from schizophrenia run at approximately $65 billion per year in the United States. Worldwide sales of leading schizophrenia medications Risperdal, from Johnson & Johnson, and Zyprexa, from Eli Lilly, each generated about $4.7 billion in 2007.

The high continued cost to society, despite the success of marketed products, indicates that some of the most important symptoms of schizophrenia, such as cognitive impairment, are poorly addressed by marketed drugs. Indeed, cognitive impairment in schizophrenia patients is a key unmet medical need, which has been recognized by the FDA and multiple other authorities.

Despite the fact that drugs with novel mechanisms have not been launched for many years, the mechanisms that cause schizophrenia have become better understood and there is a more clearly defined opportunity to develop more efficacious drugs. The pathophysiology of the disease is believed to involve excessive dopamine transmission, especially at dopamine D2 receptors, and glutamate NMDA receptor hypofunction. All marketed antipsychotics block dopamine receptors, and their antipsychotic effects are strongly associated with their antagonism of dopamine D2 receptors.

However, these drugs do not treat the cognitive deficits associated with schizophrenia and are generally associated with side effects including sedation, extrapyramidal symptoms (impairment of control of movements), and hormonal side effects such as hyperprolactinemia, and weight gain.

mGluRs & schizophrenia
ADX71149 in schizophrenia