New schizophrenia drug could treat Alzheimer’s disease

A new drug for schizophrenia, KarXT (also known as Cobenfy), which was approved by US regulators in September, could have broader implications for treating conditions like Alzheimer's disease.

KarXT, which is the first schizophrenia drug in decades with a unique mechanism of action, has sparked excitement within psychiatric medicine. This drug targets muscarinic receptors in the brain, leading to both antipsychotic and cognitive benefits, unlike traditional schizophrenia drugs that mainly block dopamine activity, Caliber.Az reports via foreign media.

KarXT’s approval has reignited interest in muscarinic drugs, with several similar treatments currently in various stages of development for conditions like schizophrenia and Alzheimer’s.

However, the development of these new drugs remains challenging. Recently, Abbvie’s muscarinic drug, emraclidine, failed to outperform a placebo in clinical trials, raising concerns about the viability of other muscarinic drugs in development. Despite this, experts like Arthur Christopoulos from Monash University remain optimistic, noting that the field is still in its early stages.

The development of KarXT faced its own challenges. Xanomeline, one of its components, was first developed in the 1990s as a potential treatment for Alzheimer's. Although it showed promise in reducing psychotic symptoms, it was abandoned due to severe side effects like nausea and vomiting. Muscarinic receptors are spread throughout the brain and body, so drugs targeting them can cause a wide range of effects.

However, in 2009, Karuna Therapeutics combined xanomeline with another compound, trospium, which prevents unwanted side effects by blocking muscarinic receptors outside the brain. This combination formed KarXT, which has shown antipsychotic and cognitive benefits in clinical trials with milder side effects than xanomeline alone.

Research suggests that KarXT’s efficacy comes from its ability to target two muscarinic receptors, M1 and M4, which are linked to cognition and antipsychotic effects, respectively. Some researchers are exploring drugs that selectively target these receptors, but this is challenging due to the similarities between all five muscarinic receptors. To overcome this, allosteric modulators, which affect muscarinic receptors from regions outside the binding sites, are being studied.

Bristol Myers Squibb, which acquired Karuna Therapeutics in 2023, is now testing KarXT in people with Alzheimer's disease to determine if it can treat Alzheimer’s-related psychosis and possibly slow cognitive decline. Muscarinic drugs also show potential in treating addiction, Parkinson’s disease, and other conditions.

While the excitement surrounding KarXT is significant, its real-world effectiveness remains uncertain. Follow-up studies indicate that while patients improved over time, a small percentage stopped taking the drug due to side effects. This highlights the need for further research to fully understand how these drugs perform in diverse real-world settings.

By Vafa Guliyeva