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KarXT by Karuna Therapeutics offers hope for improved schizophrenia management

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HQ Team,

December 18, 2023: For individuals grappling with schizophrenia, the road to treatment is often marked by a lifelong commitment to antipsychotic medications and psychotherapy. However, the existing medications come with potentially serious side effects such as drowsiness, weight gain and spasms. Many patients as a result tend to miss doses. A recent study published in The Lancet says a potential game-changer in schizophrenia treatment has emerged, providing a glimmer of hope for patients.

 KarXT’s unique approach

KarXT, developed by biotech company Karuna Therapeutics, has come up with a treatment targeting a distinct brain chemical. KarXT zeroes in on the muscarinic neurotransmitter system, linked to cognition, offering a potential avenue for reduced side effects. The traditional treatment for schizophrenia targets dopamine.

Positive outcomes

The study enrolled 252 hospitalized individuals with schizophrenia, randomly assigning them to receive either two daily capsules of KarXT or a placebo for five weeks. Encouragingly, those on KarXT exhibited fewer extremes of positive and negative symptoms associated with acute psychosis compared to the placebo group. Moreover, both groups reported similar rates of side effects, such as constipation, diarrhea, reflux, and hypertension.

Andrew Miller, Chief Operating Officer of Karuna, emphasizes the significance of this breakthrough, stating, “This represents a new option and a new approach in an area where there is still substantial need for advances in treatments.”

Neurotransmitter System: Key to success

KarXT’s deviation from the dopamine-centric approach of traditional treatments lies in its focus on muscarinic receptors in the brain, crucial for cognition. The muscarinic neurotransmitter system is associated with acetylcholine, a key player in certain cognition-related treatments for Alzheimer’s disease. Preliminary studies in patients with Alzheimer’s-related psychoses have shown potential benefits, highlighting the versatility of KarXT’s novel approach.

However, targeting muscarinic receptors posed a challenge due to their widespread presence throughout the body, leading to potential side effects. To overcome this hurdle, Karuna scientists combined their compound with another to restrict the drug’s action outside the brain, resulting in the development of KarXT.

Awaiting FDA approval

With the trial results submitted to the U.S. Food and Drug Administration (FDA), Karuna is optimistic about the potential approval of KarXT. The FDA is expected to decide by September 2024, marking a crucial milestone in the journey toward a more effective and tolerable treatment for schizophrenia.

Dopamine-centric treatment

The cornerstone of schizophrenia treatment is based on the dopamine hypothesis of schizophrenia—the theory that a dysregulated dopamine system causes the condition’s symptoms. The dopamine focus has led to antipsychotics becoming the classic treatment for schizophrenia. schizophrenia affects about 24 million people worldwide.  One in 20 people with schizophrenia takes their own life, and almost 80 percent of the sufferers are not able to lead a normal functional life.

The antipsychotic that is found to work best is clozapine, which emerged in the late 1980s, but it can have unwanted side effects, including weight gain, diabetes, and excessive sleepiness. 

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