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Quinpramine for Parkinson’s Disease

A part of Parkinson’s disease progression involves abnormal aggregation of normal brain proteins into knots of insoluble irritant material. The protein involved in many cases is alpha-synuclein. Preventing these knots starting, or stopping them increasing in size, is one possible means of treating the disease.  We have a drug candidate that prevents the proteins from grouping together on the outside of cells. The candidate is a combination of two known compounds.  It is in an early stage of pharmacological testing.

Project Description:             
The project will study our candidate drug, quinpramine, in pre-clinical models for Parkinson’s disease. First the oral dosage forms of quinpramine will be studied in pre-clinical models to determine the doses and the dosing schedule for further experiments. Next, the drug will be evaluated in a Parkinson’s disease model overexpressing alpha-synuclein. Behavioral tests will assess the effect on disease symptoms while microscopy techniques will monitor effects on alpha-synuclein, neurodegeneration and inflammation. In addition, in preparation for the further development of quinpramine, we will make early safety assessments conducted to exclude unwanted adverse effects.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
Quinpramine has the potential to be developed for the treatment of Parkinson’s disease by specifically interacting with alpha-synuclein. By doing so, the progression of the disease could be slowed down or stopped before it becomes severe.

Anticipated Outcome:          
The project should provide pre-clinical proof of concept for this molecule and prepare for the non-clinical development i.e. the assessment in regulatory-required toxicology studies as a pre-requisite for clinical testing. 

Final Outcome

Quinpramine is a candidate drug that prevents clumping of proteins such as prions and alpha-synuclein in the brains of people with Creutzfeldt-Jakob disease and Parkinson's disease (PD), respectively. We evaluated the properties and therapeutic potential of quinpramine in vitro and in vivo. We found that in pre-clinical models, once-daily (or even less frequent) oral dose of the drug is enough to maintain therapeutic levels of quinpramine in the blood and the brain. Furthermore, quinpramine was evaluated in a pre-clinical model of Parkinson's with excess of alpha-synuclein. Long-term treatment with quinpramine improved longevity and movement in the models and reduced the amount of alpha-synuclein inside brain cells. In summary, these studies further support a potential therapeutic effect of quinpramine, but additional studies are needed to prove that.

November 2014


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