We are interested in discovering drugs for treatment of central nervous system (CNS) disorders, including Alzheimer’s disease (AD), motoneuron disease (MND), traumatic brain injury (TBI), spinal cord injury (SCI) and neuropathic pain (NP). Retinoic acid (RA) signalling is important for the maintenance and regeneration of the CNS. The receptors involved in this are retinoic acid receptors (RARs) of which there are three types: alpha, beta and gamma. Our translational programs have run from bench to clinic. Work funded by the Wellcome Trust and MRC has allowed for us develop a first in class orally available RAR beta drug (KCL 286) to treat CNS disorders, where axonal outgrowth, new nerve connections and reduction of inflammation are required. This includes SCI, for which there are no treatments. We already have a multicentre phase IIA trial set up and funding is being sought from various streams.

Please see my Research Staff Profile for more detail.

Key publications:

• Goncalves et al., 2019. Regulation of Myelination by Exosome Associated Retinoic Acid Release from NG2-Positive Cells. J Neurosci.
• Goncalves et al., 2019. Novel RARβ drug demonstrates efficacy in a pre-clinical neuropathic pain model restoring multiple pathways via DNA repair mechanisms. iScience.
• Trigo et al., 2019. The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor beta signaling. FASEB J.
• Borthwick et al., 2020. Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review. Bioorg Med Chem.
• Goncalves et al., 2019. Discovery and lead optimisation of a potent, selective and orally bioavailable RARbeta agonist for the potential treatment of nerve injury. Bioorg Med Chem.

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