New orally available drug for spinal cord injury found to be safe and tolerable in healthy participants
New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has demonstrated the safety and tolerability of a new drug treatment designed as a therapeutic intervention for spinal cord injury (SCI).
The research, published in British Journal of Clinical Pharmacology, found that the KCL-286 drug – which works by activating retinoic acid receptor beta (RARb) in the spine to promote recovery - was well tolerated by participants in a Phase 1 clinical trial, with no severe side effects. Researchers are now seeking funding for a Phase 2a trial studying the safety and tolerability of the drug in those with SCI.
Global prevalence of SCI is estimated to be between 0.7 and 1.2 million cases per year, with falls and road accidents being the major causes. Despite incurring a cost of $4 billion per year in direct healthcare and indirect costs (i.e. inability to work and social care) in the US alone, there are no licensed drugs that can tackle the intrinsic failure of the adult central nervous system to regenerate, and thus remains a largely unmet clinical need.
Previous research by various groups has shown that nerve growth can be stimulated by activating the RARb2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARb2 agonist1, was developed by Professor Corcoran and team and used in a first in man study to test its safety in humans.
109 healthy males were divided into one of two trial groups; single ascending dose (SAD) adaptive design with a food interaction (FI) arm, and multiple ascending dose (MAD) arm. Participants in each arm were further divided into different dose treatments.
SAD studies are designed to establish the safe dosage range of a medicine by providing participants with small doses before gradually increasing the dose provided. Researchers look for any side effects, and measure how the medicine is processed within the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate the potential for a drug to accumulate within the body.
Researchers found that participants were able to safely take 100mg doses of KCL-286, with no severe adverse events.
Professor Jonathan Corcoran, Professor of Neuroscience and Director of the Neuroscience Drug Discovery Unit, at King’s IoPPN and the study’s senior author said, “This represents an important first step in demonstrating the viability of KCL-286 in treating spinal cord injuries. This first-in-human study has shown that a 100mg dose delivered via a pill can be safely taken by humans. Furthermore, we have also shown evidence that it engages with the correct receptor.
“Our focus can hopefully now turn to researching the effects of this intervention in people with spinal cord injuries.”
Dr. Bia Goncalves, a senior scientist and project manager of the study, and the study’s first author from King’s IoPPN said, “Spinal Cord Injuries are a life changing condition that can have a huge impact on a person’s ability to carry out the most basic of tasks, and the knock-on effects on their physical and mental health are significant.
“The outcomes of this study demonstrate the potential for therapeutic interventions for SCI, and I am hopeful for what our future research will find.”
This work was possible thanks to funding from the Medical Research Council.
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- Agonist drugs work by binding to an inactive receptor, allowing it to activate.
Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL-286, a novel RARβ agonist for treatment of spinal cord injury, in male healthy participants (DOI10.1101/2023.05.02.539081) (Maria B Goncalves, Tim Mant, Jörg Täubel, Earl Clarke, Hana Hassanin, Daryl Bendel, Henry Fok, John Posner, Jane Holmes, Adrian P Mander, Jonathan P T Corcoran) was published in British Journal of Clinical Pharmacology.
About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience
King's College London is one of the top 35 universities in the world and one of the top 10 in Europe (QS World University Rankings, 2021/22) and among the oldest in England. King's has more than 33,000 students (including more than 12,800 postgraduates) from over 150 countries worldwide, and 8,500 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research.
The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.
British Journal of Clinical Pharmacology
Method of Research
Randomized controlled/clinical trial
Subject of Research
Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL-286, a novel retinoic acid receptor-β agonist for treatment of spinal cord injury, in male healthy participants
Article Publication Date
The authors declare no competing financial interests. MBG and J.P.T.C have a matter of composition patent for KCL-286.