For people with schizophrenia, treatment is an ongoing, life-long process of antipsychotic medications and psychotherapy. Medications are key to controlling episodes, but most have serious enough side effects—including uncontrolled muscle movements, gaining weight and drowsiness—that people skip doses or decide not to take them.
In a study published Dec. 14 in the Lancet, researchers report on a promising new treatment for the psychiatric disorder that could give patients better options. KarXT, developed by biotech company Karuna Therapeutics, targets a different brain chemical than most existing schizophrenia treatments and appears to have fewer side effects.
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The study involved 252 people who were hospitalized with schizophrenia and randomly assigned to receive two capsules of KarXT, or a placebo, per day for five weeks. Those taking the drug showed fewer extremes of positive and negative symptoms associated with acute psychosis than those on placebo. Both groups has similar rates of side effects, including constipation, diarrhea, reflux and hypertension.
“This represents a new option, and a new approach in an area where there is still substantial need for advances in treatments,” says Andrew Miller, chief operating officer of Karuna.
Unlike existing schizophrenia treatments, which target the brain chemical dopamine, KarXT targets the muscarinic neurotransmitter system in the brain, which is involved in cognition. The muscarinic receptors on brain cells bind with the brain chemical acetylcholine, which is the target of certain cognition-related treatments for Alzheimer’s disease. In studies that Karuna conducted in these patients, its scientists found that patients with Alzheimer’s-related psychoses seemed to benefit as well. “By targeting a completely different neurotransmitter system, through completely different receptors, clinical data uncovered novel benefits without the problematic side effects of existing treatments,” he says.
But because muscarinic receptors are found widely throughout the body, creating a drug that targets them was challenging, since it would trigger serious side effects. To solve the problem, Karuna scientists combined its compound with another that blocked the drug from acting outside of the brain. “That enabled the development of KarXT,” Miller says.
Karuna has submitted the results of this trial as part of it request to the U.S. Food and Drug Administration for approval; the agency will make a decision by Sept. 2024.
