Latest orally available drug for spinal cord injury found to be protected and tolerable in healthy participants

Latest research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has demonstrated the protection and tolerability of a brand 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) within the spine to advertise recovery – was well tolerated by participants in a Phase 1 clinical trial, with no severe unwanted side effects. Researchers are actually looking for funding for a Phase 2a trial studying the protection 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 yr, with falls and road accidents being the key causes. Despite incurring a value of $4 billion per yr in direct healthcare and indirect costs (i.e. inability to work and social care) within the US alone, there are not any licensed drugs that may tackle the intrinsic failure of the adult central nervous system to regenerate, and thus stays a largely unmet clinical need.

Previous research by various groups has shown that nerve growth could be stimulated by activating the RARb2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARb2 agonist, was developed by Professor Corcoran and team and utilized in a primary in man study to check its safety in humans.

109 healthy males were divided into considered 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 determine the protected dosage range of a medication by providing participants with small doses before steadily increasing the dose provided. Researchers search for any unwanted side effects, and measure how the drugs is processed throughout the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate the potential for a drug to build up throughout the body.

Researchers found that participants were capable of safely take 100mg doses of KCL-286, with no severe opposed events.

Professor Jonathan Corcoran, Professor of Neuroscience and Director of the Neuroscience Drug Discovery Unit, at King’s IoPPN and the study’s senior creator said, “This represents a crucial first step in demonstrating the viability of KCL-286 in treating spinal cord injuries. This primary-in-human study has shown that a 100mg dose delivered via a pill could be safely taken by humans. Moreover, we’ve also shown evidence that it engages with the proper receptor.

Our focus can hopefully now turn to researching the consequences of this intervention in individuals with spinal cord injuries. Spinal Cord Injuries are a life changing condition that may have a big impact on an individual’s ability to perform probably the most basic of tasks, and the knock-on effects on their physical and mental health are significant.”

Dr Bia Goncalves, Study First Creator and Senior Scientist and Project Manager, King’s College London

“The outcomes of this study display the potential for therapeutic interventions for SCI, and I’m looking forward to what our future research will find.”

This work was possible due to funding from the Medical Research Council.