Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems

PLoS ONE, 2016 · DOI: 10.1371/journal.pone.0147626 · Published: January 25, 2016

Simple Explanation

Amyotrophic Lateral Sclerosis (ALS) is a devastating disease with limited treatment options. This study explores a novel approach using computational tools to identify drug combinations that can target multiple factors contributing to motor neuron death. The researchers identified two drug combinations, Alitretinoin and Pranlukast, and Alitretinoin and Mefloquine, through a systems biology approach. These combinations were then tested in an in vitro model of ALS using cultured spinal cord slices. The results showed that both drug combinations promoted neuroprotection of motor neurons and reduced microgliosis, suggesting a potential therapeutic benefit for ALS.

Study Duration

Not specified

Participants

Sprague-Dawley rat pups

Evidence Level

In vitro study

Key Findings

1
The drug combinations Alitretinoin plus Pranlukast (CD1) and Alitretinoin plus Mefloquine (CD2) were identified as potentially useful to treat ALS.
2
Both drug combinations exerted a significant neuroprotective effect on motor neuron preservation in an in vitro model of ALS.
3
The drug combinations reduced microglial reactivity, suggesting a promising approach for reducing neuroinflammation in ALS.

Research Summary

This study utilizes a systems biology approach to identify novel drug combinations for the treatment of ALS. The researchers screened existing compounds and identified Alitretinoin plus Pranlukast (CD1) and Alitretinoin plus Mefloquine (CD2) as potential candidates. In vitro experiments using spinal cord organotypic cultures demonstrated that both CD1 and CD2 exerted neuroprotective effects on motor neurons and reduced microglial reactivity, suggesting a potential therapeutic benefit for ALS. The proposed polypharmacology represents a system-based targeting approach for ALS and warrants further preclinical investigations with a perspective on clinical trials in patients.

Practical Implications

Drug Repurposing

The study identifies existing drugs that could be repurposed for ALS treatment, potentially accelerating the development of new therapies.

Multitargeted Therapy

The drug combinations target multiple pathogenic mechanisms in ALS, offering a more comprehensive approach to treatment.

Personalized Medicine

The systems biology approach could be used to identify drug combinations that are tailored to individual patients based on their specific disease characteristics.

Study Limitations

1
The study is based on in vitro experiments, and further in vivo studies are needed to confirm the findings.
2
The specific mechanisms of action of the drug combinations are not fully understood and require further investigation.
3
The study does not address the potential side effects or toxicity of the drug combinations.

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