The Crosstalk Between the Epigenome and Mitochondria in SCI

Summary

SCI is a devastating neurological disorder for which there are not yet restorative therapies. Thus, there is a need to explore new therapeutic strategies to treat SCI patients. To this end an appropriate selection and enrolment of suitable participants is crucial for the success of the therapeutic protocol. The selection of participants in SCI trials is often based on injury categories (e.g. sensorimotor complete vs incomplete), and neglects biological aspects (e.g. biomarkers released into the CSF and/or blood) that may be amenable to specific therapeutic interventions. On a biomolecular standpoint, it is renown that CNS lacks the ability to sustain a complete regenerative response after damage, which is partially due to the inability of damaged neurons to sustain an epigenetic pro-regenerative response.

The background of the present protocol study stands in pre-existing data which showed a crosstalk between the epigenome gene and mitochondria activated upon SCI. The clinical branch of this study protocol aims to investigate if and how targeted proteomic changes following the acute and chronic phase of SCI may play a role in determining the severity of neurologic impairments, as determined with ASIA gradingscale system, at the time of patients' presentation and in the conversion of ASIA grade during follow-up. A previous pilot study conducted by Wichmann et al. has shed light on proteomics after SCI enabling a profiling of inflammatory responses after spinal cord injury, timing of proteomics changes involved in inflammatory responses and differences between proteins title in CSF and peripheral blood. On the other hand, authors failed to prove a correlation between inflammatory proteins expression and timing of expression and neurologic status. However, previous studies proved that proteome expression variations SCI-induced can be detected into patients' CSF and serum and that biomarkers released into the CSF and/or blood may provide a plethora of information as to the patients' biological response to SCI. These samples may contain a unique fingerprint that can be used by scientists and clinicians to elucidate the mechanisms underlying irreversible central nervous system (CNS) degeneration following SCI. This could allow treatments to target specific molecules which promote CNS degeneration. Within this context the identification of prognostic biomarkers of SCI will help to assign SCI patients to the correct therapeutic treatment that, in association with canonical therapies, may synergistically act to improve functional recovery.

The aim of the present study is to investigate the presence of prognostic markers in SCI patient-derived serum and CSF with respect to a control group of healthy patients.

Conditions

• Injury, Spinal Cord

Interventions

OTHER

Data collection

The data to be collected are the following: * Demographic data: gender and age of the patient at diagnosis of SCI; * Drug assumption and drug abuse at the time of SCI; * A complete assessment of patients' comorbidities; * Complete neurological examination on admission and at 6-8 months follow-up according to ASIA protocol; * Neuro-radiological data: spinal CT and MRI performed within 48 hours of admission to document the type, level and extent of the lesion of the spine and the spinal cord; * CSF pressure, chemical and biological markers; * Serum chemical and biological markers; * Data coming from surgical procedure: type of decompression, type of stabilization, extension of the stabilization, surgical approach, staged surgery, timing of surgery, length of surgery, eventual intraoperative, postoperative or long-term surgical-related complications \[13\]; * Data on hospitalization: length of stay, hospital-acquired infections, any adverse event occurred during hospitalisation.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  lead OTHER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-08-30

Primary Completion

2025-08-30

Completion

2026-08-30