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Clinical Trial B: Azathioprine immunosuppression and disease modification in Parkinson’s disease (AIM-PD)

Strand B: Clinical Translational Research

Clinical Programme 2 - Early Phase Trials

Clinical Trial B: Azathioprine immunosuppression and disease modification in Parkinson’s disease (AIM-PD)

Lead/Co-lead: Dr Caroline H. Williams-Gray/Professor Roger A. Barker

Aim

Immune activation is strongly implicated in a number of neurodegenerative diseases, including Parkinson’s disease (PD) and related Parkinson-Plus disorders. Our own work has demonstrated not only that there is a genetic link between the immune system and PD risk, but also a more active immune response with raised inflammatory markers in the blood being associated with more rapid progression of the disease.  This study will test the hypothesis that suppressing the peripheral immune response in PD with azathioprine is an effective disease-modifying strategy. This may ultimately lead to the clinical adoption of a highly cost effective therapy to delay disability and prevent progression to the some of the most feared complications of PD including severe balance problems and dementia, for which we currently have no effective treatments. This therapeutic strategy may also be beneficial for other Parkinson–Plus disorders which share common disease mechanisms.

 

Methods

  • We will perform a double-blind randomised controlled trial of azathioprine versus placebo in a cohort of early PD patients at high risk of rapid disease progression to provide proof of concept for immunosuppression as a disease-modifying strategy.
  • We will evaluate the effect of azathioprine on markers of immune activation in blood and CSF and on PET neuroimaging to provide proof of mechanism.

 

Related publications

  • Williams-Gray, C. H., Wijeyekoon, R., Yarnall, A. J., Lawson, R. A., Breen, D. P., Evans, J. R., Cummins, G. A., Duncan, G. W., Khoo, T. K., Burn, D. J., Barker, R. A., & ICICLE-PD Study group. (2016). Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD). Mov Disord, 31(7), 995-1003. doi:10.1002/mds.26563
  • Saiki M, Baker A, Williams-Gray CH, Foltynie T, Goodman RS, Taylor CJ, Compston DA, Barker RA, Sawcer SJ, Goris A. (2010). Association of the human leucocyte antigen region with susceptibility to Parkinson's disease. Journal of neurology, neurosurgery, and psychiatry; 81(8):890-1.
  • Williams-Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker RA. Evolution of cognitive dysfunction in an incident Parkinson's disease cohort. (2007). Brain;130(Pt 7):1787-98.
  • Williams-Gray CH, Evans JR, Goris A, Foltynie T, Ban M, Robbins TW, Brayne C, Kolachana BS, Weinberger DR, Sawcer SJ, Barker RA. (2009). The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. Brain; 132(Pt 11):2958-69.
  • Williams-Gray CH, Mason SL, Evans JR, Foltynie T, Brayne C, Robbins TW, Barker RA. (2013).  The CamPaIGN study of Parkinson's disease: 10-year outlook in an incident population-based cohort. Journal of neurology, neurosurgery, and psychiatry; 84(11):1258-64.
  • Velseboer DC, de Bie RM, Wieske L, Evans JR, Mason SL, Foltynie T, Schmand B, de Haan RJ, Post B, Barker RA, Williams-Gray CH. (2016). Development and external validation of a prognostic model in newly diagnosed Parkinson disease. Neurology; 86(11):986-93.
  • Liu, G., Locascio, J. J., Corvol, J. C., Boot, B., Liao, Z., Page, K., Franco, D., Burke, K., Jansen, I. E., Trisini-Lipsanopoulos, A., Winder-Rhodes, S., Tanner, C. M., Lang, A. E., Eberly, S., Elbaz, A., Brice, A., Mangone, G., Ravina, B., Shoulson, I., Cormier-Dequaire, F., Heutink, P., van Hilten, J. J., Barker, R. A., Williams-Gray, C. H., Marinus, J., Scherzer, C. R. (2017). Prediction of cognition in Parkinson's disease with a clinical-genetic score: a longitudinal analysis of nine cohorts. Lancet Neurol, 16(8), 620-629. doi:10.1016/S1474-4422(17)30122-9.
  • Williams-Gray, C. H., & Barker, R. A. (2017). Parkinson disease: Defining PD subtypes - a step toward personalized management? Nat Rev Neurol, 13(8), 454-455. doi:10.1038/nrneurol.2017.98
  • Barker, R. A., & Williams-Gray, C. H. (2016). Review: The spectrum of clinical features seen with alpha synuclein pathology. Neuropathol Appl Neurobiol, 42(1), 6-19. doi:10.1111/nan.12303

Dr Caroline H. Williams-Gray; MRC Clinician Scientist & Honorary Consultant Neurologist

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Professor Roger A. Barker

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