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Funded Studies

Validating BMPs as novel drug candidates for Parkinson’s disease

Study Rationale: Neurotrophic factors are prime candidates for the development of disease-modifying therapies, based on their properties to restore and maintain the functional integrity of neurons that are dysfunctional but not lost. Clinical trials demonstrated that these proteins are generally safe, however, they have not been able to meet their primary endpoint, which has been associated to the inability of the so far tested neurotrophic factors to protect dopaminergic neurons against alpha-synuclein-induced neurotoxicity. Recently, we discovered that the neurotrophic factors bone morphogenetic proteins (BMP) 5/7 protect dopaminergic neurons against alpha-synuclein protein induced neurotoxicity when simultaneously applied with alpha-synuclein and thus represent new potential drug candidates for PD.

Hypothesis: We hypothesize that BMPs show therapeutic effects not only against the overexpressed α-synuclein protein but also against the highly toxic α-synuclein preformed fibrils. Moreover, we hypothesize that BMPs also protect dopaminergic neurons when applied after alpha-synuclein preformed fibrils have caused neural damage.  

Study Design: To recapitulate major neuropathological changes occurring in Parkinson’s disease, we will expose pre-clinical models to alpha-synuclein preformed fibrils. We will then study the therapeutic potential of BMPs when simultaneously applied with the preformed fibrils. To recapitulate the clinical reality in which Parkinson’s disease patients are treated after the onset of motor symptoms, we will apply BMPs after the preformed fibrils have caused motor symptoms in mice. Finally, we will compare the neuroprotective effects of BMPs to GDNF, which has been the best investigated neurotrophic factor for Parkinson’s disease treatment so far.

Impact on Diagnosis/Treatment of Parkinson’s disease: Data from the preclinical tests will be essential to assess the potential of BMPs for further evaluation in preclinical and clinical trials.

Next Steps for Development: If we can confirm our hypothesis, a next step toward clinical application of BMPs will include studies assessing the optimal application of BMPs.


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