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.
Second-generation (atypical) antipsychotics are the first-line treatment for schizophrenia. There are significant side effects that occur in patients receiving atypical antipsychotics, including weight gain, diabetes mellitus, hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects, and cataracts.
Symptoms of schizophrenia may result from increased subcortical release of dopamine, which increases activity of D1 receptor expressing neurons and decreases activity of D2 receptor expressing neurons in striatum, increasing the amount of “noise” propagated through the basal ganglia circuit. Atypical antipsychotics block both serotonin 5-HT2a and dopamine D2 receptors, but do not directly alter activity in D1 receptor expressing neurons. Therefore, MapLight is focusing its therapeutic strategy on targeting both D1 and D2 expressing neuronal circuits, using non-dopaminergic targets in these neurons.
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 atypical antipsychotics.