Schizophrenia drug could cure Alzheimer’s disease

This innovation revived research in muscarinicsa class of drugs that have fallen by the wayside in the treatment of brain diseases.

The development of KarXT began with research into xanomeline, a compound that was shown in the 1990s to reduce psychotic symptoms in people with Alzheimer’s disease. However, xanomeline caused side effects such as nausea and vomiting due to its effects on muscarinic receptors throughout the body. To avoid these effects, Karuna Therapeutics combined xanomeline with trospium, a compound that blocks these receptors outside the brain, minimizing side effects in the body.

This approach, known as KarXT, has been shown to have antipsychotic and cognitive effects in patients with schizophrenia, with fewer side effects than the original treatment, reports a paper in the journal Nature.

The approval of this drug in the United States meant something for Eduard Vieta, a researcher at the Biomedical Research Center for Mental Health Network (CIBERSAM). Head of the Psychiatry and Psychology Service at the Hospital Clinic of Barcelona and Professor at the University of Barcelona, ​​“an important step in the treatment of schizophrenia, since it is the first drug that acts not directly on dopaminergic receptors, but on muscarinic ones. Speaking to Science Media Center, Vieta said that this feeling, although acetylcholine and dopamine are related, represents a very relevant innovation because it is a mechanism the actions of modern drugs and the side effect profile, which is also different, may represent a good alternative for patients who cannot tolerate currently used drugs.

In addition, the effect size in the acute phase and the results of the extended study regarding long-term safety and effectiveness are also positive. Once approved, clinical experience will indicate the extent to which it represents a true advance in clinical practice in this disease, which requires new approaches.

The success of KarXT has renewed interest in muscarinicswhich are known to influence cognitive processes and reward circuits in the brain. The researchers noted that the drug may have applications beyond schizophrenia, particularly in the treatment of psychosis associated with Alzheimer’s disease and disorders such as bipolar disorder.

In addition, muscarinic M1 receptors, which are associated with cognitive ability, are being investigated for the treatment of cognitive impairment in patients with Alzheimer’s disease. The hope is that drugs targeting these receptors could slow the progression of the neurodegenerative disease.

Despite the enthusiasm KarXT has generated, researchers caution that developing new drugs is a long and complex process.

Thus, according to José García-Valdecasas, deputy secretary of the board of the Spanish Association of Neuropsychiatry, “a new drug with a new mechanism of action appears, which is good in principle, but in these cases we must avoid creating an image of excessive effectiveness or excessive expectations in the face of novelty. Just because something is new doesn’t necessarily mean it’s better.. “You have to focus on the research and the data available.”

Same as placebo

For example, a recent clinical trial of the drug emraclidineanother muscarinic drug for the treatment of schizophrenia failed to outperform placebo, raising questions about the effectiveness of other similar drugs. Scientists are exploring allosteric modulators that more specifically target muscarinic receptors, with the goal of reducing side effects and increasing effectiveness.

The future of KarXT and other muscarinic drugs remains uncertain. Although clinical trials have shown promising results, the real test of these drugs will be their effectiveness in real worldwhere patients are not isolated in controlled conditions. Researchers continue to monitor the effects of KarXT in outpatients with schizophrenia and are also studying its effect on Alzheimer’s disease.

Although the development of these treatments is still in the early stages, progress in the use of muscarinic drugs to treat brain diseases offers new hope for the treatment of complex diseases such as schizophrenia and Alzheimer’s disease.

However Scientists emphasize the need for more research to to understand how these drugs affect patients in the long term and whether they can actually slow or stop the progression of diseases such as Alzheimer’s disease.