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A novel RARb agonist for spinal cord injury receives funding for a phase 1 trial from the MRC-DPFS

Posted on 28/09/2017

Orally available retinoic acid receptor b agonist for the treatment of spinal cord injuries- MRC-DPFS funded Phase 1 trial (£2.2 million)

Spinal cord injury (SCI) is a disabling and irreversible condition that has high economic and social costs. There are currently more than 2.5 million people worldwide who are living with paralysis as SCI.

Since 2010 Professor Jonathan Corcoran has obtained Wellcome Trust funding (SDDI awards) to develop a drug discovery programme at King’s College London, and together with Dr. Bia Goncalves has identified and optimised a novel series of orally bioavailable and selective retinoic acid receptor (RAR) b agonists. A fully, validated pre-clinical package has been carried out with the lead candidate, KCL-286 and MHRA acceptance for a FIM study has been obtained. More recently, Professor Corcoran, Dr. Goncalves and Professor Tim Mant, have been awarded £2.2 million from the DPFS-MRC scheme, to carry out the Phase 1 trial. The trial will bring together the BRC and the Surrey CRC and is due to commence in early 2018.

There are presently no available treatments for SCIs and the current most promising therapeutic approaches are not without limitations as they rely on combinational therapy and intrathecal administration such as cell based treatments with growth factors. In contrast, KCL-286 is orally available and has demonstrated efficacy in models of SCI. Several regenerative mechanisms have been identified in both the neurons and the glial cells.

Retinoid signalling is mediated by nuclear receptors. RARb has genomic and non-genomic effects and thus it can regulate a plethora of pathways. A specific RARb agonist can singularly produce an effective therapy that would otherwise need several points of intervention from different drugs. KCL-286 induces axonal regeneration with functional recovery in two SCI models: sensory root avulsion and thoracic spinal contusion. The mode of action of this agonist involves modulation of both neurons and glial cells and their cross-talk during regeneration. The multifactorial facet of the effects of KCL-286 confers it a unique and very attractive therapeutic not only for SCIs but potentially for a broad spectrum of neuronal injuries such as stroke, neuropathies and traumatic brain injury.

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