INTRODUCTION
RA, cord injury, road accidents
The reported global prevalence of spinal cord injury (SCI) is between 0.7 and 1.2 million incident cases per year with falls and road accidents being the major causes.The retinoic acid (RA) signalling pathway has been shown to be involved in axonal outgrowth. The pathway consists of the nuclear receptors, the RA receptors (RARs) and the retinoid x receptors (RXRs) of which there are 3 types—α, β and γ—and various subtypes. An RAR associates with an RXR and the heterodimer binds at RA response element (RARE) of target genes and transcription occurs once a retinoid binds (Figure KCL‐286 transcriptional neuronal signalling. KCL‐286 binds to a retinoic acid receptor (RAR)β2/retinoid x receptor (RXR) heterodimer located at a retinoic acid response element (RARE). This results in activation of transcriptional pathways required for axonal regeneration.KCL‐286, also known as C286, is an oral RARβ agonist with multifactorial reparative effects in the CNS.To determine the risk: benefit ratio of KCL‐286 it is necessary to establish the safety and pharmacokinetic (PK) profile in healthy volunteers and then progress to establish efficacy in SCI patients. Here we report a Phase I safety and PK study of KCL‐286 and show that it is a safe and well‐ tolerated drug with a satisfactory PK profile that engages with its receptor in white blood cells (WBCs), where RARβ2 is expressed,