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Common Anti-Diarrhea Medication May Help Treat Core Symptoms of Autism

Researchers searched existing drugs, looking for potential treatments for the core symptoms of autism spectrum disorder. The most promising one they found is called loperamide, better known by the brand name Imodium, which is commonly used for diarrhea.

Study is the first to use protein interaction networks to study whether existing drugs could treat autism, finding potential in a common antidiarrheal drug.

There are currently no effective treatments for the core symptoms of autism spectrum disorder (ASD), such as difficulties with socializing and communicating. A new study uses a computer-based protein interaction network to identify whether existing drugs could provide a new treatment approach. The researchers discovered that a common anti-diarrheal drug may have potential in treating the social difficulties associated with ASD.

Can you teach an old drug new tricks? Drug treatments for the core symptoms of autism spectrum disorder (ASD) are not currently available. However, could an existing drug provide a new treatment, even if it previously had no association with ASD? This was the question asked by a new study that was published on September 12 in the journal Frontiers in Pharmacology. The researchers used a computer model that encompasses proteins involved in ASD and the way they interact.

They identified potential candidates to treat ASD by looking at how different drugs affected proteins in the system. A commonly used antidiarrheal drug called loperamide was the most promising candidate, and the researchers have an interesting hypothesis about how it may work to treat ASD symptoms. Some of the most common symptoms of ASD involve difficulties with social interaction and communication.

“There are no medications currently approved for the treatment of social communication deficits, the main symptom in ASD,” said Dr. Elise Koch. She is the lead author of the study and a Postdoctoral Fellow at the Institute of Clinical Medicine at the University of Oslo. “However, most adults and about half of children and adolescents with ASD are treated with antipsychotic drugs, which have serious side effects or lack efficacy in ASD.”

Repurposing drugs as new treatments

In an effort to find a new way to treat ASD, the researchers turned to drug repurposing. This involves exploring existing drugs as potential treatments for a different condition. There are many benefits to this approach, as there is often extensive knowledge about existing drugs in terms of their safety, side effects, and the biological molecules that they interact with inside the body.

Loperamide is a medicine to treat short-term diarrhea or irritable bowel syndrome (IBS). It is more commonly known by the brand name Imodium, and is available over-the-counter (nonprescription). It is on the World Health Organization’s List of Essential Medicines.

To identify new treatments for ASD, the scientists used a computer-based protein interaction network. Such networks encompass proteins and the complex interactions between them. It is important to account for this complexity when studying biological systems, as affecting one protein can often have knock-on effects elsewhere.

The investigators constructed a protein interaction network that included proteins associated with ASD. By investigating existing drugs and their interaction with proteins in the network, the team identified several candidates that counteract the biological process underlying ASD.

The most promising drug is called loperamide, which is commonly used for diarrhea. Although it might seem strange that an anti-diarrheal drug could treat core ASD symptoms, the scientists have developed a hypothesis about how it may work.

From an upset gastrointestinal system to ASD

Loperamide binds to and activates a protein called the μ-opioid receptor, which is normally affected by opioid drugs, such as morphine. Along with the effects that you would normally expect from an opioid drug, such as pain relief, the μ-opioid receptor also affects social behavior.

In previous studies, genetically engineered mice that lack the μ-opioid receptor demonstrated social deficits similar to those seen in ASD. Interestingly, drugs that activate the μ-opioid receptor helped to restore social behaviors.

These results in mice highlight the tantalizing possibility that loperamide, or other drugs that target the μ-opioid receptor, may represent a new way to treat the social symptoms present in ASD. However, further work is required to test this hypothesis. In any case, the current study demonstrates the power of assuming that old drugs may indeed learn new tricks.   

Reference: “Drug repurposing candidates to treat core symptoms in autism spectrum disorder” by Elise Koch and Ditte Demontis, 12 September 2022, Frontiers in Pharmacology.
DOI: 10.3389/fphar.2022.995439

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