Centre for Discovery Brain Sciences
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Dr Stuart Cobb

Our lab uses a broad range of technologies to develop novel treatments for neurodevelopmental disorders based on a deep understanding of the molecular pathology.

 

Dr Stuart Cobb

Reader

  • Hugh Robson Building
  • 15 George Square
  • EH8 9XD

Contact details

Personal profile

  • 2017 - present: Simons Fellow and Reader in Neuroscience, University of Edinburgh
  • 2002 - 2017: Lecturer, Sn. Lecturer, Reader, University of Glasgow
  • 1999 - 2002: RSE Caledonian Research Fellow, University of Glasgow
  • 1996 - 1999: RA, University of Edinburgh
  • 1993 - 1996: DPhil in Neuroscience, University of Oxford

Research Themes

Research

Abnormalities in brain development, once thought to be irreversible in adults, are assumed to underlie a range of autism, intellectual disability and epilepsy disorders. There is growing evidence that reversing the underlying molecular deficits can result in substantial improvements in function and this knowledge is in turn changing the way we view and envisage treating such disorders in the future.

The aim of my laboratory is to understand the tractability of neurodevelopmental disorders (NDDs) to therapeutic intervention. This includes gaining an understanding of those aspects of NDDs that genuinely result from aberrant early brain development to features that result from ongoing dysfunction within the mature nervous system. This is important not only for a fundamental understanding of the pathophysiology but also in terms of windows of opportunity for treatment.

A major focus of our efforts is to develop gene therapy for Rett Syndrome and related disorders. Our laboratory was the first to report the ameliorative effect of gene therapy in mice modelling the disorder. Projects going forward include:

  1. A programme to develop next generation Rett syndrome gene therapy cassettes for enhanced efficacy and safety.
  2. Developing RNA and splicing-based approaches to bypass disease-causing mutations in neurodevelopmental and epilepsy disorders (Rett syndrome, CDKL5 deficiency, Dravet syndrome).
  3. Testing the reversibility of neurological dysfunction and testing classical gene transfer and editing approaches in other related neurodevelopmental disorders.
Expression of gene therapy vector derived MeCP2 in cortical neuron
Expression of gene therapy vector derived MeCP2 in cortical neuron

Funding

Lab Members

  • Kamal Gadalla, Postdoctoral Fellow
  • Ralph Hector, Postdoctoral Fellow
  • Paul Ross, Postdoctoral Fellow
  • Sophie Thomson, Postdoctoral Fellow
  • Stephanie Mearns, Research Technician
  • Marie Bowers, Research Technician
  • Zoe Sawitzki, Research Technician

Collaborations

Selected Publications

Hector, R.D., Kalscheuer V.M., Hennig, F., Leonard H., Downs J., Clarke A., Benke, T.A., Armstrong J., Pineda. M., Bailey M.E.S., Cobb S. (2017) CDKL5 variants: improving our understanding of a rare neurological disorder. Neurology genetics, 3 (6):e200. doi: 10.1212/NXG.0000000000000200

Tillotson, R., Selfridge, J., Koerner, M.V., Gadalla, K.E., Guy, J., De Sousa, D., Hector, R.D., Cobb, S.R. and Bird, A. (2017) Radically shortened MeCP2 reverses Rett syndrome-like neurological defects. Nature, 550, 398-401.

Bahey, N.G., Gadalla, K.K.E., McGonigal, R., Bailey, M.E.S., Edgar, J.M., and Cobb, S.R. (2017) Reduced axonal diameter of peripheral nerve fibres in a mouse model of Rett syndrome. Neuroscience, 358, 261-8.

Gadalla, K.K., Vudhironarit, T., Hector, R.D., Sinnett, S.E., Bahey, N.G., Bailey, M.E.S., Gray, S.J. and Cobb, S.R. (2017) Development of a novel AAV gene therapy cassette with improved safety features and efficacy in a mouse model of Rett syndrome. Molecular therapy methods and clinical development. 5 :180-190. doi: 10.1016/j.omtm.2017.04.007.

Leonard, H., Cobb, S., and Downs, J. (2017) Clinical and biological progress over 50 years in Rett syndrome. Nature Reviews Neurology, 13(1), pp. 37-51. (doi:10.1038/nrneurol.2016.186) (PMID:27934853)

Ross, P.D., Guy, J., Selfridge, J., Kamal, B., Bahey, N., Tanner, E., Gillingwater, T., Jones, R., Loughrey, C.M., McCarroll, C.S., Bailey, M.E.S., Bird, A., Cobb, S.R. (2016) Tissue-specific reactivation of Mecp2 in mice reveals both brain and peripheral phenotypes. Human Molecular Genetics, (doi:10.1093/hmg/ddw269) (Early Online Publication)

Hector, R., Dando, O., Landsberger, N., Kilstrup-Nielsen, C., Kind, P., Bailey, M.E.S., Cobb, S. (2016) Characterisation of CDKL5 transcript isoforms in human and mouse. PLOS one. http://dx.doi.org/10.1371/journal.pone.0157758

Cobb, S. R. (2015) Cognitive disorders: deep brain stimulation for Rett syndrome. Nature, 526(7573), pp. 331-332. (doi:10.1038/526331a) (PMID:26469040)

Booker, S. A., Pires, N., Cobb, S., Soares-da-Silva, P., and Vida, I. (2015) Carbamazepine and oxcarbazepine, but not eslicarbazepine, enhance excitatory synaptic transmission onto hippocampal CA1 pyramidal cells through an antagonist action at adenosine A1 receptors. Neuropharmacology, 93, pp. 103-115. (doi:10.1016/j.neuropharm.2015.01.019) (PMID:25656478)

Kamal, B., Russell, D., Payne, A., Constante, D., Tanner, K. E., Isaksson, H., Mathavan, N., and Cobb, S. R. (2015) Biomechanical properties of bone in a mouse model of Rett syndrome. Bone, 71, pp. 106-114. (doi:10.1016/j.bone.2014.10.008) (PMID:25445449) (PMCID:PMC4289916)