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A New Schizophrenia Treatment: KarXT

A New Schizophrenia Treatment: KarXT

Schizophrenia, a severe, long-term mental health condition, affects approximately 1 in 300 people worldwide. The symptoms, including hallucinations, delusions, muddled thoughts, and social withdrawal, can be debilitating. While antipsychotic drugs are commonly used to treat the condition, they don’t work for everyone. This is where KarXT, a new combination drug developed by Karuna Therapeutics Inc., comes into play.

The Science Behind KarXT

KarXT is a combination therapy that combines two different drugs, xanomeline and trospium chloride. These drugs target receptors in the brain and body associated with the cholinergic neurotransmitter system, which plays a key role in learning, memory, digestion, control of heartbeat, blood pressure, movement, and many other functions.

There are two types of cholinergic receptors, nicotinic and muscarinic. In KarXT, xanomeline activates muscarinic receptors in the brain, whereas trospium chloride blocks activation of muscarinic receptors in the body. This dual action is what makes KarXT a promising new treatment for schizophrenia.

The Journey of KarXT

Xanomeline was originally developed to treat Alzheimer’s disease by US pharmaceutical company, Eli Lilly and Company. While it was shown to improve cognition and some of the behavioral symptoms of Alzheimer’s in trials, its development was stopped as some people experienced problematic side effects. These side effects were caused by muscarinic receptor activation in the body.

Karuna’s founder, Andrew Miller, anticipated that combining trospium chloride with xanomeline would reduce these side effects and hypothesized this new therapy would reduce psychosis in people living with schizophrenia. And it worked.

Clinical Trials and Results

Karuna was funded in 2015 and 2018 to undertake a Phase 1 and then Phase 2 trial of KarXT. In the Phase 1 trial, KarXT was shown to be safe and well-tolerated with a 50% reduction in side effects compared to xanomeline alone in healthy adults.

Results from the Phase 2 trial in people with schizophrenia were also positive, and in 2019, Karuna announced that KarXT led to a statistically significant reduction in psychotic symptoms in people living with schizophrenia. Seven years after the initial investment, results from a Phase 3 trial of KarXT in schizophrenia have found the treatment to be promising.

The Future of KarXT

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.

By targeting a completely different neurotransmitter system, through completely different receptors, clinical data uncovered novel benefits without the problematic side effects of existing treatments. Karuna has submitted the results of this trial as part of its request to the U.S. Food and Drug Administration for approval; the agency will make a decision by Sept. 2024.

In conclusion, KarXT represents a significant breakthrough in the treatment of schizophrenia. Its unique approach and promising results from clinical trials offer hope for millions of people living with this condition. As we await the FDA’s decision, the medical community watches with bated breath, hopeful that KarXT will usher in a new era in schizophrenia treatment.


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