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Funded Studies

Testing of Ambroxol in the Thy1-Alpha-Synuclein Pre-clinical Model of Parkinson's disease

Biochemical evidence suggests that blocking the maturation of a natural enzyme, glucocerebrosidase (GCase), can cause the build-up of alpha-synuclein deposits in neurons.  Such deposits are pathological hallmarks of Parkinson’s disease.  Compelling genetic evidence has also implicated GCase in Parkinson’s disease.  Ambroxol is an existing drug that can “chaperone” GCase to its mature form where it no longer promotes pathological deposit formation.  We intend to test whether ambroxol can ameliorate Parkinson’s disease-like symptoms and pathology in a pre-clinical model of Parkinson’s disease.

Project Description:
Thy1-Alpha-Synuclein pre-clinical models have been genetically engineered to “over-express” the alpha-synuclein gene in the brain.  These pre-clinical models recapitulate during their growth and development a number of motor, non-motor, and neuropathological deficits characteristic of Parkinson’s disease.  We will feed the pre-clinical models ambroxol and periodically test them for improvements in Parkinson’s disease-like deficits – this will include measuring motor skills such as balance and coordination, and testing for olfactory dysfunction and cognitive deficits.  Results with ambroxol-fed pre-clinical models will be compared with results of identical tests on “control” Thy1-Alpha-Synuclein pre-clinical models that have not been fed the drug.  At the end of the experiment, the brains of both ambroxol-fed and control pre-clinical models will be examined for neuropathological signs of Parkinson’s disease such as alpha-synuclein deposits, dopamine depletion, and inflammation.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Parkinson’s disease is a very complex disease and has traditionally been treated with therapies aimed at treating the symptoms rather than the underlying causes; this is understandable since so little is known about the actual causes.  Recent research has indicated that GCase deficiency may be a fundamental contributing factor to Parkinson’s disease, thus intervening to correct such a deficiency using pharmacological chaperones like ambroxol might represent a new and powerful therapeutic approach.

Anticipated Outcome:
Our goal is to re-purpose ambroxol as a drug for Parkinson’s disease (ambroxol is currently used to treat airway disorders).  Positive efficacy data in the Thy1-Alpha-Synuclein pre-clinical would motivate and support efforts to move forward with clinical trials of ambroxol in Parkinson’s disease patients.  Demonstration of efficacy in Parkinson’s disease patients will likely lead to ambroxol being approved as a therapeutic for Parkinson’s disease.


  • Robert F. Johnston, MBA

    Monmouth Junction, NJ United States

  • Marie-Francoise Chesselet, MD, PhD

    Los Angeles, CA United States

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