On Monday 18th April, the 3rd symposium on Chemical and Biological Therapeutic Approaches to Neurological Disorders took place at Burlington House in London. Dr Paul Beswick and I (Tristan Reuillon) represented the Sussex Drug Discovery Centre (SDDC) at this one day conference, organised by the Royal Society of Chemistry. Paul gave a talk on the use of structural biology for the design of ligands for glutamate ionotropic receptors, an approach which has been and is being used on different projects at the SDDC, while I presented a poster on recent developments in the field of AMPA receptor positive allosteric modulators.
Some of the leading researchers in the field of neuroscience were presenting, such as Dr Eric Karran, former head of research at Alzheimer Research UK now at AbbVie or Prof John Hardy from UCL, recent winner of the Breakthrough Prize in Life Sciences for his pioneering research into the genetic causes of Alzheimer’s disease (AD). Dementia was the major focus of the symposium, with Dr Eric Karran introducing the statistics on AD and giving a detailed overview of the different theories believed to underlie AD (amyloid-beta (Aβ) and tau pathologies). According to Dr Karran the readouts of some critical clinical trials on AD drugs within the next two years will be extremely important to understand if the drug discovery efforts have been heading in the right direction and to guide further the current research on dementia. Prof John Hardy presented the genetic causes behind AD and amyloid deposition, with an emphasis on some specific proteins, such as TREM2, which represent very attractive drug discovery targets. Prof Nigel Hooper from the University of Manchester presented research focussed on Aβ, trying to identify what forms of Aβ oligomers and fibrils are neurotoxic and trying to link the alpha-secretase ADAM10 with Aβ production. Finally Dr Suchira Bose from Eli Lilly gave an in-depth analysis of the tau pathophysiology and different modulations of this physiological pathway which could lead to novel therapeutic approaches to AD.
Other neurological disorders were also discussed during the symposium. Dr Hasane Ratni from Roche presented the discovery of RG7800, a drug currently tested in phase II clinical trials for the treatment of Spinal Muscular Atrophy, a rare neurodegenerative disease affecting mainly children. RG7800 acts as a SMN2 splicing modifier. Dr Richard Mead from the University of Sheffield talked about his current research on Motor Neuron Disease, also termed Amyotrophic Lateral Sclerosis, with a focus on the NRF2-ARE pathway, an indicator and modulator of oxidative stress in neurodegeneration. Different attempts to identify activators of this pathway, such as apomorphine, were discussed. The presentation of Dr Paul Beswick on glutamate potentiators was centred on the identification of novel drugs to treat the cognitive dysfunction associated with Schizophrenia, a major symptom, for which there is a clear unmet medical need. Finally, Prof Kristian Stromgaard from the University of Copenhagen, presented a few drug discovery approaches that his group has undertaken to disrupt protein-protein interactions in the CNS, such as the PSD-95-NMDA interaction. Owning to the lack of success in identifying small molecule hits, his research has focussed on peptidomimetics, which are surprisingly brain penetrant and are currently in preclinical development.
I found this symposium extremely interesting, with some fantastic and innovative research being disclosed, and would highly recommend it for anyone interested in neuroscience research. I hope to have given you through this blog article a flavour of the different topics which were discussed on that day and maybe tempted you to attend the 4th symposium in this series which will take place next year.
Blog written by Tristan Reuillon