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Cambridge Centre for Parkinson-Plus


Strand A: Scientific Discovery Programmes

Lead: Professor Giovanna Mallucci

Our Scientific Discovery Programmes will deliver an advanced understanding of disease mechanisms and capitalise on advances in biomarker and clinical trial methodology; these programmes will discover novel therapeutics that feed directly into our Clinical Translational Programmes.


Research Programme 1: Mechanisms of trazodone action and PERK activation for drug treatment of Parkinson-Plus diseases

The recent discovery of the protective effects of the licensed anti-depressant drug trazodone through its effect on the unfolded protein response (UPR) forms the starting point to expand drug discovery for these Parkinson-Plus disorders. The proposed pre-clinical work will increase our understanding of

  • the action of trazodone in neuroprotective UPR signalling to further drive drug discovery
  • how the UPR signalling is activated and regulated in these disorders.

This Research Programme is directly linked to an early phase clinical trial within the Clinical Translational Programmes.

For further details please click here.


Research Programme 2: Identification of therapeutic targets in synucleinopathy causes of Parkinson-Plus and Parkinson's disease

The accumulation of the protein called α-synuclein is a hallmark of Parkinson's disease and some forms of Parkinson-Plus disease. Reducing the misfolding, and aggregation of α-synuclein, and increasing its clearance, offer new therapeutic strategies for these conditions.

This programme will identify genes and biological pathways that can reduce α-synuclein levels and which are amenable to existing drugs or novel compounds, to discover and develop new treatments for patients with these disorders.

For further details please click here.


Research Programme 3: Defining the role of somatic genetic mutations in Parkinson-Plus diseases

We will identify mutations in key proteins that determine the clinical features of Parkinson-Plus disorders, including mutations in body tissues rather than being inherited. This approach will define potential novel targets for drug development to:

  • reduce the risk of Parkinson-Plus disease
  • modify the clinical phenotype (the age of onset, and pattern of symptoms)

The genetic studies also aim to improve early diagnosis, at a time when new treatments are most likely to be effective; and identify specific subgroups of patients with somatic mutations in specific genes, thus providing a new approach to develop gene-specific personalized therapies.

For further details please click here.