Peptidergic drugs for the treatment of traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a devastating medical condition that has an enormous socioeconomic impact because it affects more than 10 million people annually worldwide and is associated with high rates of hospitalization, mortality and disability. Although TBI survival has improved continuously for decades, particularly in developing countries, implementation of an effective drug therapy for TBI represents an unmet clinical need. All confirmatory trials conducted to date with drugs targeting a single TBI pathological pathway failed to show clinical efficacy, probably because TBI pathophysiology involves multiple cellular and molecular mechanisms of secondary brain damage. According to current scientific evidence of the participation of peptide-mediated mechanisms in the processes of brain injury and repair after TBI, peptidergic drugs represent a multimodal therapy alternative to improve acute outcome and long-term recovery in TBI patients. Preliminary randomized-controlled clinical trials and open-label studies conducted to date with the peptidergic drug Cerebrolysin® (Ever Neuro Pharma GmbH, Unterach, Austria) and with the endogenous neuropeptides progesterone and erythropoietin, showed positive clinical results. Cerebrolysin-treated patients had a faster clinical recovery, a shorter hospitalization time and a better long-term outcome. Treatment with progesterone showed advantages over placebo regarding TBI mortality and clinical outcome, whereas erythropoietin only reduced mortality. Further validation of these promising findings in confirmatory randomized-controlled clinical trials is warranted. This article reviews the scientific basis and clinical evidence on the development of multimodal peptidergic drugs as a therapeutic option for the effective treatment of TBI patients.