REPURPOSING OF NICLOSAMIDE, AN ANTHELMINTIC, IN AUTISM SPECTRUM DISORDER BY TARGETING ERK/MAPK SIGNALING PATHWAY IN RATS

Introduction

 

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition that affects a growing number of individuals worldwide. Despite significant advancements in research, effective treatments for ASD remain elusive. In recent years, researchers have explored the potential of repurposing existing drugs for ASD, a strategy that can accelerate drug development and reduce costs. One such drug, niclosamide, has garnered attention for its potential to target specific molecular pathways involved in ASD.

 

Niclosamide: A Versatile Drug with Potential

 

Niclosamide, originally developed as an anthelmintic drug to treat tapeworm infections, has demonstrated a remarkable versatility in its therapeutic applications. It has been investigated for its potential benefits in various diseases, including cancer, diabetes, and neurodegenerative disorders. Recent studies have highlighted the anti-inflammatory and neuroprotective properties of niclosamide, making it an attractive candidate for exploring its potential in ASD.

 

The Role of the ERK/MAPK Signaling Pathway in ASD

 

The ERK/MAPK signaling pathway is a critical intracellular signaling cascade involved in regulating a wide range of cellular processes, including cell proliferation, differentiation, and survival. Dysregulation of this pathway has been implicated in several neurodevelopmental disorders, including ASD. Studies have shown that aberrant activation of the ERK/MAPK pathway can lead to impaired neuronal development, synaptic dysfunction, and behavioral abnormalities.

 

Niclosamide’s Potential to Target the ERK/MAPK Pathway

 

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Niclosamide has been shown to inhibit the activation of the ERK/MAPK pathway, suggesting that it could potentially ameliorate the symptoms of ASD by targeting this molecular target. By interfering with the signaling cascade, niclosamide may help to restore normal neuronal function and improve behavioral outcomes in individuals with ASD.

 

Key Findings from Recent Research

 

A recent study published in August 2024 investigated the effects of niclosamide on ASD-like behaviors in rats. The researchers found that chronic administration of niclosamide significantly improved social interaction, communication, and repetitive behaviors in the rats. Furthermore, the drug was well-tolerated, with no adverse side effects observed.

 

Potential Benefits of Niclosamide for ASD

 

Based on the findings of this study and previous research, niclosamide may offer several potential benefits for individuals with ASD, including:

  • Improved social interaction: Niclosamide could help individuals with ASD develop stronger social skills and engage more effectively with others.
  • Reduced repetitive behaviors: The drug may help alleviate repetitive behaviors, such as stereotypies or rituals, which can be a significant source of distress for individuals with ASD.
  • Enhanced communication: Niclosamide could improve language and communication skills, making it easier for individuals with ASD to express themselves and interact with their environment.

 

Future Directions and Considerations

 

While the results of this study are promising, further research is needed to fully understand the mechanisms of action of niclosamide in ASD and to evaluate its efficacy and safety in human clinical trials. Additionally, it is essential to consider the potential long-term effects of niclosamide on brain development and function.

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Conclusion

 

Repurposing niclosamide for ASD represents a promising avenue for exploring new therapeutic options for this complex condition. By targeting the ERK/MAPK signaling pathway, niclosamide may offer a novel approach to addressing the core symptoms of ASD. As research continues to advance, it is hoped that niclosamide will eventually become a valuable tool in the treatment of ASD.

 

Additional Considerations

 

  • Personalized Medicine: Given the heterogeneity of ASD, it is important to explore personalized approaches to niclosamide treatment, taking into account individual genetic, environmental, and clinical factors.
  • Combination Therapies: Niclosamide could potentially be combined with other therapeutic interventions, such as behavioral therapy or educational support, to enhance its effectiveness.
  • Safety and Tolerability: Further studies are needed to assess the long-term safety and tolerability of niclosamide in individuals with ASD, especially in children and adolescents.

 

By addressing these considerations, researchers can continue to advance our understanding of niclosamide’s potential role in ASD treatment and develop more effective and personalized therapeutic strategies for individuals with this condition.

 

Source:

https://www.sciencedirect.com/science/article/abs/pii/S0014299924005910

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