Schizophrenia is a complex psychiatric disorder characterized by 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 30% of schizophrenia patients have no response to treatment and an additional 30% only have a partial response to current treatment options, leaving a substantial portion of the population with urgent unmet need.

Dopaminergic 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, and sexual side effects. The use of dopaminergic 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 multiple populations of neurons that become dysfunctional during schizophrenia without directly blocking dopamine receptors, MapLight’s ML-007/PAC therapeutic is aiming to improve efficacy without the side effects seen with dopaminergic atypical antipsychotics.


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