Combatting Alzheimer’s - new drugs with great promise in the fight against neurodegeneration
Discovery and commercialisation of an entirely new drug for the treatment of Alzheimer’s disease
Professor Wischik and his group discovered the first compounds to prevent accumulation of a brain protein called tau, a process associated with the onset of Alzheimer’s disease and other degenerative diseases of the brain.
The findings derived from several years of studies at the Laboratory of Molecular Biology at Cambridge. From 1998, in Aberdeen, the group continued with the development of cellular and transgenic mouse models of tau protein accumulation, and formed TauRx Therapeutics Ltd which now has about 60 employees and researchers. Evidence of clinical efficacy in the largest phase 2 clinical trial for Alzheimer’s disease has led to confirmatory phase 3 trials being undertaken by TauRx and which are planned for completion in 2016. Researchers used cellular and animal models to:
demonstrate the mechanism of action;
produce pharmaceutical drugs for clinical trials; and
develop novel molecules binding to abnormal tau for diagnosis of Alzheimer's disease.
The research of Aberdeen scientists has brought in funding of over £20 million to the University.
Wischik, CM, Edwards, PC, Lai, RYK, Roth, M, Harrington, CR (1996) Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc. Natl. Acad. Sci. USA 93:11213-11218.
Wischik C.M., Wischik D.J., Storey J.M.D., Harrington C.R. (2010) Rationale for tau aggregation inhibitor therapy in Alzheimer's disease and other tauopathies. In Emerging drugs and targets for Alzheimer's disease. Volume 1: Beta-amyloid, tau protein and glucose metabolism, ed. A. Martinez. pp. 210-232. RSC Drug Discovery Series Cambridge: Royal Society of Chemistry
Wischik, CM., Harrington, CR. & Storey, JMD. (2014). 'Tau-aggregation inhibitor therapy for Alzheimer's disease'. Biochemical Pharmacology, vol 88, no. 4, pp. 529-539. • Baddeley, TC., McCaffrey, J., Storey, JMD., Cheung, JKS., Melis, V., Horsley, D., Harrington, CR. & Wischik, CM. (2015). 'Complex Disposition of Methylthioninium Redox Forms Determines Efficacy in Tau Aggregation Inhibitor Therapy for Alzheimer's Disease'. Journal of Pharmacology and Experimental Therapeutics, vol 352, no. 1, pp. 110-118.
Wischik, CM., Staff, RT., Wischik, DJ., Bentham, P., Murray, AD., Storey, JMD., Kook, KA. & Harrington, CR. (2015). 'Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease'. Journal of Alzheimer's Disease, vol 44, no. 2, pp. 705-720.
Harrington, CR., Storey, JMD., Clunas, S., Harrington, KA., Horsley, D., Ishaq, A., Kemp, SJ., Larch, CP., Marshall, C., Nicoll, SL., Rickard, JE., Simpson, M., Sinclair, JP., Storey, LJ. & Wischik, CM. (2015). 'Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease'. The Journal of Biological Chemistry, vol 290, no. 17, pp. 10862-10875.
Melis, V., Magbagbeolu, M., Rickard, JE., Horsley, D., Davidson, K., Harrington, KA., Goatman, K., Goatman, EA., Deiana, S., Close, SP., Zabke, C., Stamer, K., Dietze, S., Schwab, K., Storey, JMD., Harrington, CR., Wischik, CM., Theuring, F. & Riedel, G. (2015). 'Effects of oxidized and reduced forms of methylthioninium in two transgenic mouse tauopathy models'. Behavioural Pharmacology, vol 26, no. 4, pp. 353-368.
Melis, V., Zabke, C., Stamer, K., Magbagbeolu, M., Schwab, K., Marshall, P., Weh, RW., Bachmann, S., Deiana, S., Moreau, PH., Davidson, K., Harrington, KA., Rickard, JE., Horsley, D., Garman, R., Mazurkiewicz, M., Niewiadomska, G., Wischik, CM., Harrington, CR., Riedel, G. & Theuring, F. (2015). 'Different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for Alzheimer's disease and frontotemporal lobar degeneration'. Cellular and Molecular Life Sciences, vol 72, no. 11, pp. 2199-2222.