Disease-modifying approaches for Parkinson disease

Simon JG Lewis
Med J Aust 2018; 208 (9): . || doi: 10.5694/mja17.01135
Published online: 9 April 2018

While a cure might be far off, concerted efforts targeting disease modification are ramping up

We need to find a cure for a disease for which we do not know the cause, have no diagnostic test, and strongly suspect is multifactorial, leading to significant heterogeneity. Two hundred years after its initial description, this is precisely where we find ourselves with Parkinson disease. By the time a patient is first diagnosed, there has been significant cell death and, as such, it seems likely that at best any disease-modifying therapy will arrest or, more likely, only slow continued cell death. While data from the recent phase 2 study repurposing the diabetes treatment exenatide offer hope,1 the field has previously been disappointed by a catalogue of trials that have failed to translate into clinical practice. While clearly too brief, it is hoped that this article will provide the reader with some appreciation of this rapidly expanding topic.

  • Brain and Mind Centre, University of Sydney, Sydney, NSW



Simon Lewis is part of the ForeFront project team and is supported by a National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship (no. 1110414). ForeFront is a large collaborative research group dedicated to the study of neurodegenerative diseases and is funded by grants from the NHMRC (no. 1037746), Dementia Research Team (no. 1095127), NeuroSleep Centre of Research Excellence (no. 1060992), ARC Centre of Excellence in Cognition and its Disorders Memory Program (CE110001021) and the Sydney Research Excellence Initiative 2020.

Competing interests:

No relevant disclosures.

  • 1. Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet 2017; 390: 1664-1675.
  • 2. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers 2017; 3: 17013.
  • 3. Prusiner SB, Woerman AL, Mordes DA, et al. Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci U S A 2015; 112: E5308-E5317.
  • 4. Recasens A, Dehay B, Bové J, et al. Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 2014; 75: 351-362.
  • 5. Sulzer D, Alcalay RN, Garretti F, et al. T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature 2017; 546: 656-661.
  • 6. Postuma RB, Anang J, Pelletier A, et al. Caffeine as symptomatic treatment for Parkinson disease (Café-PD): a randomized trial. Neurology 2017; 89: 1795-1803.
  • 7. Villafane G, Thiriez C, Audureau E, et al. High-dose transdermal nicotine in Parkinson’s disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study. Eur J Neurol 2017; 25: 120-127.
  • 8. Mittal S, Bjørnevik K, Im DS, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science 2017; 357: 891-898.
  • 9. Parkinson Study Group QE3 Investigators, Beal MF, Oakes D, Shoulson I, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol 2014; 71: 543-552.
  • 10. Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators, Kieburtz K, Tilley BC, Elm JJ, et al. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA 2015; 313: 584-593.
  • 11. NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators. Pioglitazone in early Parkinson’s disease: a phase 2, multicentre, double-blind, randomised trial. Lancet Neurol 2015; 14: 795-803.
  • 12. Cereda E, Barichella M, Cassani E, et al. Clinical features of Parkinson disease when onset of diabetes came first: a case-control study. Neurology 2012; 78: 1507-1511.
  • 13. Athauda D, Foltynie T. Protective effects of the GLP-1 mimetic exendin-4 in Parkinson’s disease. Neuropharmacology 2017. doi:10.1016/j.neuropharm.2017.09.023 [Epub ahead of print].
  • 14. Bennett LL, Mohan D. Gaucher disease and its treatment options. Ann Pharmacother 2013; 47: 1182-1193.
  • 15. Espay AJ, Schwarzschild MA, Tanner CM, et al. Biomarker-driven phenotyping in Parkinson’s disease: a translational missing link in disease-modifying clinical trials. Mov Disord 2017; 32: 319-324.


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