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Antidiarrheal drugs may help treat key symptoms of autism – Neuroscience News

Summary: Loperamide, a common antidiarrheal drug, may help treat the main symptoms associated with autism spectrum disorders. The drug activates the μ-opioid receptor, helping to improve social behaviors.

Source: Borders

Can you teach new tricks to an old drug? Although drug treatments for the core symptoms of Autism Spectrum Disorders (ASD) are not currently available, could an existing drug provide a new treatment, even if previously unrelated to ASD?

This is the question posed by a new study published in the journal Frontiers in pharmacology.

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

By examining 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 might work to treat ASD symptoms. Some of the most common symptoms of ASDs involve difficulties with social interaction and communication.

“There are currently no drugs approved for the treatment of social communication deficits, the primary symptom of ASDs,” said Dr Elise Koch of the University of Oslo, lead author of the study. “However, most adults and about half of children and adolescents with ASD are treated with antipsychotic medications, 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, researchers have turned to drug repurposing, which involves exploring existing drugs as potential treatments for a different condition. The approach has many advantages, as there is often extensive knowledge about existing drugs in terms of safety, side effects, and the biological molecules they interact with in the body.

To identify new treatments for ASD, the researchers used a protein interaction computing network. These networks encompass proteins and the complex interactions between them. It is important to consider this complexity when studying biological systems because affecting one protein can often have repercussions elsewhere.

A commonly used antidiarrheal drug called loperamide was the most promising candidate, and the researchers have an interesting hypothesis about how it might work to treat ASD symptoms. Image is in public domain

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

The most promising drug is loperamide, commonly used for diarrhea. Although it may seem strange that an anti-diarrheal drug could treat the main symptoms of ASD, researchers have developed a hypothesis about how it works.

From a disrupted gastrointestinal system to ASD

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

In previous studies, genetically engineered mice lacking the μ-opioid receptor exhibited social deficits similar to those seen in ASD. Interestingly, drugs that activate the μ-opioid receptor helped 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 novel way to treat the social symptoms found in ASD, but further work is needed to test this hypothesis. Either way, the current study demonstrates the power of assuming that old drugs can indeed learn new tricks.

About this Neuropharmacology and ASD Research News

Author: Colm Gorey
Source: Borders
Contact: Colm Gorey – Frontiers
Image: Image is in public domain

See also

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Original research: Free access.
“Candidates for Redirecting Medication to Treat Core Symptoms of Autism Spectrum Disorders” by Elise Koch et al. Frontiers in pharmacology


Summary

Candidates for drug redirection to treat core symptoms of autism spectrum disorders

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

To identify potential drugs for reuse to effectively treat core ASD symptoms, we investigated ASD risk genes within protein-protein interaction networks of gene products. We first defined an ASD network from network-based analyzes and identified approved drugs known to interact with proteins in this network. Subsequently, we assessed whether these drugs could modify ASD-associated gene expression perturbations in ASD network genes.

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

Four drugs with significant signs (p < 0.05) opposite gene expression disturbances in the drug compared to TSA were identified: loperamide, bromocriptine, drospirenone and progesterone. These drugs act on the biological systems related to ASD, indicating that these drugs could effectively treat the main symptoms of ASD.

Based on our bioinformatics analyzes of ASD genetics, we pre-screen potential drug redirection candidates that warrant clinical translation to treat core ASD symptoms.

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