Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence

Romeo-Guitart, David; Forés, Joaquím; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valérie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

doi:10.1038/s41598-018-19767-3

Cited by 59 publications

(71 citation statements)

References 65 publications

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“…NeuroHeal was in silico designed to promote neuroprotection, enhance axonal regeneration, and reduce neuropathic pain after nerve root avulsion [17,33]. We confirmed its neuroprotective…”

Section: Discussionsupporting

confidence: 57%

“…NeuroHeal was in silico designed to promote neuroprotection, enhance axonal regeneration, and reduce neuropathic pain after nerve root avulsion [17,33]. We confirmed its neuroprotective effect in different in vivo models of motoneuron death after PNI [16,17], and we also tested its ability to increase motor axonal regeneration [22]. Nonetheless, its effects in the sensory system after nerve trauma remained elusive.…”

Section: Discussionmentioning

confidence: 65%

“…To test whether NeuroHeal increases the regeneration of sensory axons, as it does for motor ones [17,21,22], we performed in vitro and in vivo experiments. We treated collagen-embedded DRG explants with NeuroHeal, Acamprosate or Ribavirin, and analyzed the number of neurites sprouting out from the explants and neurite length.…”

Section: Neuroheal Enhances Regeneration Of Sensory and Motor Axonsmentioning

confidence: 99%

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NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

Casas

2020

Cells

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Peripheral nerve injury (PNI) leads to the loss of motor, sensory, and autonomic functions, and often triggers neuropathic pain. During the last years, many efforts have focused on finding new therapies to increase axonal regeneration or to alleviate painful conditions. Still only a few of them have targeted both phenomena. Incipient or aberrant sensory axon regeneration is related to abnormal unpleasant sensations, such as hyperalgesia or allodynia. We recently have discovered NeuroHeal, a combination of two repurposed drugs; Acamprosate and Ribavirin. NeuroHeal is a neuroprotective agent that also enhances motor axon regeneration after PNI. In this work, we investigated its effect on sensory fiber regeneration and PNI-induced painful sensations in a rat model of spare nerve injury and nerve crush. The follow up of the animals showed that NeuroHeal treatment reduced the signs of neuropathic pain in both models. Besides, the treatment favored sensory axon regeneration, as observed in dorsal root ganglion explants. Mechanistically, the effects observed in vivo may improve the resolution of cell-protective autophagy. Additionally, NeuroHeal treatment modulated the P2X4-BDNF-KCC2 axis, which is an essential driver of neuropathic pain. These data open a new therapeutic avenue based on autophagic modulation to foster endogenous regenerative mechanisms and reduce the appearance of neuropathic pain in PNI.

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“…NeuroHeal was in silico designed to promote neuroprotection, enhance axonal regeneration, and reduce neuropathic pain after nerve root avulsion [17,33]. We confirmed its neuroprotective…”

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 65%

Section: Neuroheal Enhances Regeneration Of Sensory and Motor Axonsmentioning

confidence: 99%

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NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

Casas

2020

Cells

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“…The Therapeutic Performance Mapping System (TPMS) is a tool that creates mathematical models of a drug/pathology response to explain a clinical outcome or phenotype 4,[9][10][11][12][13][14] . We applied TPMS to the drug-indication pair sacubitril/valsartan and HF: for the drug we retrieved and manually curated the sacubitril/valsartan targets from DrugBank 17 , PubChem 18 , STITCH 19 , SuperTarget 20 and hand curated literature revision, while for the indication we used the proteins associated with the phenotype from the BED.…”

Section: Tpms Modelling Of Phenotypesmentioning

confidence: 99%

“…It has been broadly used in the last years in different clinical areas and with different objectives. 4,[10][11][12][13][14] The TPMS incorporates data from massive databases publicly available and experimental information obtained for the diseases and drugs under study to generate multiple models of potential MoAs.…”

Section: Introductionmentioning

confidence: 99%

TPMS technology to infer biomarkers of macular degeneration prognosis in in silico simulated prototype-patients under the study of heart failure treatment with sacubitril and valsartan

Jorba

Aguirre‐Plans

Segú-Vergés

et al. 2019

Preprint

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Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of drug(s) in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalised medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. This is achieved by (1) modelling the responses in human with an accurate description of the protein networks and (2) applying a Multilayer Perceptron-like and sampling method strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a range of mechanism of action models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their relationship with macular degeneration (a common/recurrent adverse effect). We found that a lower response in terms of heart failure treatment is more associated to macular degeneration development, although good response mechanisms can also associate to the adverse effect. A set of 30 potential biomarkers are proposed to identify mechanisms (or patients) more prone to suffering macular degeneration when presenting good heart failure response. As each molecular mechanism can be particular not only of cells but also individuals, we conclude that the study of the collection of models generated using TPMS technology can be used to detect adverse effects personalized to patients.

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Preventive Strategies for Chemotherapy-Induced Peripheral Neuropathy

Nielsen

Herrstedt

2021

Diagnosis, Management and Emerging Strategies for Chemotherapy-Induced Neuropathy

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Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence

Cited by 59 publications

References 65 publications

NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

TPMS technology to infer biomarkers of macular degeneration prognosis in in silico simulated prototype-patients under the study of heart failure treatment with sacubitril and valsartan

Preventive Strategies for Chemotherapy-Induced Peripheral Neuropathy

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