Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome

Antonio Gatto, Lavinia Capossela, Giorgio Conti, Gemma Eftimiadi, Serena Ferretti, Luigi Manni, Antonietta Curatola, Benedetta Graglia, Lorenzo Di Sarno, Maria Lucia Calcagni, Daniela Di Giuda, Stefano Cecere, Domenico Marco Romeo, Marzia Soligo, Enzo Picconi, Marco Piastra, Giacomo Della Marca, Susanna Staccioli, Antonio Ruggiero, Fabrizio CocciolilloSilvia Maria Pulitano', Antonio Chiaretti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

BackgroundSevere traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS.MethodsChildren with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale.ResultsThree children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported.ConclusionThese promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaBiology Direct
Volume18
DOI
Stato di pubblicazionePubblicato - 2023

Keywords

  • Human-recombinant nerve growth factor
  • Intranasal administration
  • Traumatic brain injury
  • Unresponsive wakefulness syndrome

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