Journal article

Receptor-ligand supplementation via a self-cleaving 2A peptide-based gene therapy promotes CNS axonal transport with functional recovery

Tasneem Z Khatib, Andrew Osborne, Sujeong Yang, Zara Ali, Wanyi Jia, Ilya Manyakin, Katie Hall, Robert Watt, Peter S Widdowson, Keith R Martin



Gene replacement approaches are leading to a revolution in the treatment of previously debilitating monogenic neurological conditions. However, the application of gene therapy to complex polygenic conditions has been limited. Down-regulation or dysfunction of receptor expression in the disease state or in the presence of excess ligand has been shown to compromise therapeutic efficacy. Here, we offer evidence that combined overexpression of both brain-derived neurotrophic factor and its receptor, tropomyosin receptor kinase B, is more effective in stimulating axonal transport than either receptor administration or ligand administration alone. We also show efficacy in experimental glaucoma and..

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Awarded by Wellcome Trust

Funding Acknowledgements

This work was supported by grants from Fight for Sight, Addenbrooke's Charitable Trust, the Cambridge Eye Trust, the Jukes Glaucoma Research Fund, Quethera Ltd., Alzheimer's Research UK, Gates Cambridge Trust, and a core support grant from the Wellcome Trust (104001/Z/14/Z) and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute.