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Anti-diarrhea Medication May Help Treat Core Autism Symptoms – Neuroscience News

Summary: Loperamide, a common anti-diarrhea medication, could help treat core symptoms associated with autism spectrum disorder. The drug activates the μ-opioid receptor, helping to improve social behaviors.

Source: Frontiers

Can you teach an old drug new tricks? Although drug treatments for the core symptoms of autism spectrum disorder (ASD) are not currently available, 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 in the journal Frontiers in Pharmacology.

The researchers used a computer model that encompasses proteins involved in ASD and the way they interact.

By looking at how different drugs affected proteins in the system, they identified potential candidates to treat it. 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 in 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 of the University of Oslo, lead author on the study. “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, which involves exploring existing drugs as potential treatments for a different condition. The approach has plenty of benefits, as there is often extensive knowledge about existing drugs in terms of their safety, side-effects and the biological molecules that they interact with in the body.

To identify new treatments for ASD, the researchers 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.

this shows a child playing with blocksA 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. Image is in the public domain

The researchers 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 biological process underlying ASD.

The most promising drug is called loperamide, which is commonly used for diarrhea. While it might seem strange that an anti-diarrheal drug could treat core ASD symptoms, the researchers 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, but 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. 

Abstract

Drug repurposing candidates to treat core symptoms in autism spectrum disorder

Autism spectrum disorder (ASD) is characterized by high heritability and clinical heterogeneity. The main core symptoms are social communication deficits. There are no medications approved for the treatment of these symptoms, and medications used to treat non-specific symptoms have serious side effects.

To identify potential drugs for repurposing to effectively treat ASD core symptoms, we studied ASD risk genes within networks of protein-protein interactions of gene products. We first defined an ASD network from network-based analyses, and identified approved drugs known to interact with proteins within this network. Thereafter, we evaluated if these drugs can change ASD-associated gene expression perturbations in genes in the ASD network.

This was done by analyses of drug-induced versus ASD-associated gene expression, where opposite gene expression perturbations in drug versus ASD indicate that the drug could counteract ASD-associated perturbations.

Four drugs showing significant (p < 0.05) opposite gene expression perturbations in drug versus ASD were identified: Loperamide, bromocriptine, drospirenone, and progesterone. These drugs act on ASD-related biological systems, indicating that these drugs could effectively treat ASD core symptoms.

Based on our bioinformatics analyses of ASD genetics, we shortlist potential drug repurposing candidates that warrant clinical translation to treat core symptoms in ASD.

Source neurosciencenews.com

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