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Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration.

Authors
  • Romeo-Guitart, David1
  • Casas, Caty1
  • 1 Institut de Neurociències (INc) and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB) & Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Barcelona, Spain. , (Spain)
Type
Published Article
Journal
Neural Regeneration Research
Publisher
Medknow Publications
Publication Date
Jul 01, 2019
Volume
14
Issue
7
Pages
1122–1128
Identifiers
DOI: 10.4103/1673-5374.251187
PMID: 30804234
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Peripheral nerve injuries caused by accidents may lead to paralysis, sensory disturbances, anaesthesia, and lack of autonomic functions. Functional recovery after disconnection of the motoneuronal soma from target tissue with proximal rupture of axons is determined by several factors: motoneuronal soma viability, proper axonal sprouting across inhibitory zones and elongation toward specific muscle, effective synapse contact rebuilding, and prevention of muscle atrophy. Therapies, such as adjuvant drugs with pleiotropic effects, that promote functional recovery after peripheral nerve injury are needed. Toward this aim, we designed a drug discovery workflow based on a network-centric molecular vision using unbiased proteomic data and neural artificial computational tools. Our focus is on boosting intrinsic capabilities of neurons for neuroprotection; this is in contrast to the common approach based on suppression of a pathobiological pathway known to be associated with disease condition. Using our workflow, we discovered neuroheal, a combination of two repurposed drugs that promotes motoneuronal soma neuroprotection, is anti-inflammatory, enhances axonal regeneration after axotomy, and reduces muscle atrophy. This drug discovery workflow has thus yielded a therapy that is close to its clinical application.

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