Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

Abstract

Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

• Authors: David Romeo-Guitart, Joaquim Forés, Mireia Herrando-Grabulosa, Raquel Valls, Tatiana Leiva-Rodríguez, Elena Galea, Francisco González-Pérez, Xavier Navarro, Valerie Petegnief, Assumpció Bosch, Mireia Coma, José Manuel Mas, Caty Casas
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 1879 (01 30 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29382857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents

Topics

• Algorithms
• Animals
• Artificial Intelligence
• Cell Line
• Female
• Machine Learning
• Mice
• Nerve Regeneration (drug effects)
• Neuroprotective Agents (pharmacology)
• Peripheral Nervous System Diseases (drug therapy)
• Radiculopathy (drug therapy)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects)
• Spinal Cord (drug effects)
• Spinal Nerve Roots (drug effects)
• Wounds and Injuries (drug therapy)