Schizophrenia is a serious disorder that causes a range of problems with thinking, behavior, and emotions. People with schizophrenia experience an altered reality, e.g., seeing/hearing things that aren’t there (hallucinations) or believing things that aren’t true (delusions), which can be both distressing and disabling. Patients with schizophrenia also experience cognitive dysfunction, such as difficulty judging how to make appropriate decisions. Approximately 60% of people with schizophrenia have no response or only a partial response to the available standard of care treatments, leaving a substantial portion of the population with urgent unmet need.

Second-generation dopaminergic (D2) atypical antipsychotics are the most commonly prescribed treatment options and help manage some of the symptoms. There are significant side effects and safety issues that can occur in patients receiving dopaminergic atypical antipsychotics, including weight gain, diabetes, metabolic disturbances, QTc interval prolongation, myocarditis, and sexual side effects. The use of D2 atypical antipsychotics can also lead to tardive dyskinesia, a movement disorder.

MapLight is focusing its strategy on addressing the positive, negative, and cognitive symptoms of schizophrenia by targeting M1 and M4 muscarinic receptors without direct targeting of dopaminergic receptors. Deficits in M1 receptors are linked to schizophrenia, and M1 receptors directly regulate neural circuits known to be important in both psychosis and cognition. M4 receptors regulate a complementary neural circuit known to be important in psychosis. 

By targeting both populations of neurons that become dysfunctional during schizophrenia without directly blocking dopamine D2 receptors, MapLight’s ML-007 therapeutic is aiming to improve efficacy without the side effects seen with dopaminergic atypical antipsychotics.

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