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Our researchers have been granted 600K euros from EU’s Horizon 2020 Framework Programme to join in a multi-centre initiative studying a new drug for Parkinson's disease

CDNF is a secreted neurotrophic and stress-protective factor with a very different mode of action compared to conventional neurotrophic factors, and a highly potent molecule with a unique structure.

The three-year project for Laura Parkkinen's group is part of the first clinical study of CDNF (Cerebral Dopamine Neurotrophic Factor) in Parkinson's disease. CDNF, patented worldwide by Herantis Pharma, a Finnish pharmaceutical company, will be administered directly into the brains of 18 Parkinson's disease patients. This will be achieved using a device specially designed for such a procedure by Renishaw in the UK. Implanting this device requires a procedure similar to Deep Brain Stimulation, a common treatment for Parkinson's disease.

Currently there are no drugs that slow or stop the progression of Parkinson's disease, or treat the debilitating non-motor symptoms such as sleep disturbance, depression, anxiety and cognitive impairment. CDNF has great promise to address these two major unmet clinical needs. 
- Dr Laura Parkkinen

CDNF is a novel neurotrophic factor (a molecule that supports the growth, survival, and differentiation of developing and mature neurons). Its mechanism of action is clearly distinct from the conventional neurotrophic factors (e.g. glial cell-derived neurotrophic factor GDNF). Its discovery in 2007 led to cutting-edge molecular neurobiology research by Professor Mart Saarmaat at the University of Helsinki.

Most notably, in the recent monkey model of Parkinson's disease, the intermittent intracerebral infusions of CDNF protein remarkably restored the motor function in parallel by restoration of dopaminergic neurons in the nigrostriatal pathway, suggesting a strong potential for disease modification.

CDNF-infused monkeys also showed remarkable improvement in non-motor functions, such as anxious behaviour and reduced motivation. This was the first time that a neurotrophic factor in an animal model of Parkinson's disease showed an improvement of non-motor symptoms that are not alleviated by any current Parkinson's drugs.

What does CDNF do?

Misfolded and aggregated α-synuclein (aSyn) is a major component of Lewy bodies (abnormal clumps of protein that develop inside nerve cells in Parkinson's disease). Its accumulation disturbs proteostasis, elicits endoplasmic reticulum (ER) stress and finally triggers neuronal death in Parkinson's diesease. A significant portion of CDNF is localised in the ER lumen and unregulated by ER stress. CDNF has a unique mechanism of action, closely associated with preventing cell death and alleviation of ER stress, possibly via directly modulating the ER stress markers. There may also be molecular interplay between CDNF and aSyn, as CDNF was recently shown in a cull culture study to protect dopaminergic neurons against toxicity caused by aSyn oligomers.

The expression of CDNF and ER stress markers has mostly been analysed in animal models and very little is known about their levels in the human brain. Laura Parkkinen's group will collaborate with University of Helsinki to characterise expression levels of CDNF and ER stress markers in the brain tissue of patients at different stages of Parkinson's disease and in healthy age-matched controls. 

CDNF and ER stress markers will also be analysed in cerebrospinal fluid samples from the Oxford Parkinson’s Disease Centre's 'Discovery' study, in order to determine the potential of ER stress markers as target engagement biomarkers for CDNF.

These two studies will be carried out together, measuring the aggregation propensity of aSyn in the brain and cerebrospinal fluid using a novel technique, real-time quaking-induced conversion (RT-QuIC). This is another potential biomarker for Parkinson's disease that Laura’s group helped to develop.

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