Abstract
Despite promising advances in the medical management of spinal cord injury (SCI), there is still no available effective therapy to repair the neurological damage in patients who experience this life-transforming condition. Recently, we performed a phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone (GH) treatment in incomplete chronic traumatic spinal cord injury. The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo slightly improves the SCI individual motor score. Moreover, we found that an intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals. To understand the possible mechanisms of the improvement due to GH treatment (motor score) and due to rehabilitation (functional outcome), we used a proteomic approach. Here, we used a multiple proteomic strategy to search for recovery biomarkers in blood plasma with the potential to predict response to somatropin treatment and to delayed intensive rehabilitation. Forty-six patients were recruited and followed for a minimum period of 1 year. Patients were classified into two groups based on their treatment: recombinant somatropin (0.4 mg) or placebo. Both groups received rehabilitation treatment. Our strategy allowed us to perform one of the deepest plasma proteomic analyses thus far, which revealed two proteomic signatures with predictive value: (i) response to recombinant somatropin treatment and (ii) response to rehabilitation. The proteins implicated in these signatures are related to homeostasis, inflammation, and coagulation functions. These findings open novel possibilities to assess and therapeutically manage patients with SCI, which could have a positive impact on their clinical response.
Highlights
The annual incidence of traumatic spinal cord injury (SCI) in Spain is estimated at 1000 cases, with the vast majority caused by traffic accidents (48%), followed by falls (21%) and sport injuries (14.6%) [1]
We sought to evaluate whether protein alterations could identify those SCI individuals who will respond to somatropin or reahabilitation treatment
No curative treatment yet exists for SCI, and rehabilitation is the only therapeutic option that can contribute to functional improvement in patients
Summary
The annual incidence of traumatic spinal cord injury (SCI) in Spain is estimated at 1000 cases, with the vast majority caused by traffic accidents (48%), followed by falls (21%) and sport injuries (14.6%) [1]. The most common medical classification to characterize SCI is the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) to classify subjects using the ASIA Impairment Scale (AIS) and the neurological level of SCI (the more caudal neurological level with normal neurological function). There is no treatment available for SCI once it is established, and rehabilitation is the only therapy for functional improvement. The life-changing consequences, along with the high social cost and the lack of treatment options make the study of SCI pathophysiology an important scientific and medical objective [3]
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