The Michael J. Fox Foundation for Parkinson's Research Foundation (MJFF) and the Silverstein Foundation for Parkinson's disease with GBA will fund the study 'Therapeutic target of GCase enzyme in Parkinson's disease with novel pharmacological chaperons (MJFF-16182)' that directs the Dra. Marta Martínez Vicente, principal investigator of the Vall d'Hebron Research Institute's (VHIR) http://en.vhir.org/portal1/grup-equip.asp?t=enfermedades-neurodegenerativas-&s=recerca&contentid=186912 Neurodegenerative Diseases group.The total grant of this call is about 3 million dollars, of which almost 500,000 correspond to the VHIR study.The projects selected through this joint financing program are intended to better understand the effect of GBA mutations on Parkinson's disease and to advance the development of treatments. Mutations in GBA are the most common genetic risk factor in Parkinson's disease and are present in 10% of the patients. Study of new pharmacological chaperones aimed to the glucocerebrosidase protein (GCase)People who have mutations in the GBA gene have a higher chance of developing Parkinson's disease (PD). The GBA gene encodes the glucerebrosidase (GCase) protein, an enzyme located inside the lysosomes, small intracellular vesicles in charge of the cellular cleaning mechanism. Changes in GCase affect several important cellular mechanisms and may contribute to neurodegeneration. To recover GCase activity, "we propose to use small molecules called non-competitive pharmacological chaperones that specifically bind to GCase and help the mutant protein to recover its structure and stability, and consequently its activity", explains Dr. Marta Martínez.This project is being developed in collaboration with the Gain Therapeutics company, focusing on the development of non-competitive pharmacological chaperones. They have been able to design more than 400 potential non-competitive GCase chaperones. The researchers, after having carried out an initial selection through biophysical and cellular trials, chose a few compounds to be tested in cellular and animal models of Parkinson's disease in order to Select a candidate drug for future clinical studies."By using this therapeutic channeling strategy, our goal is to develop and validate new pharmacological chaperones for GBA with a therapeutic effect in Parkinson's disease. Our compounds have been designed to cross he blood-brain barrier and are non-inhibitory chaperones, offering a wider therapeutic window", she says."If we get it, we will select a GBA chaperone as a candidate drug to participate in clinical trials for the treatment of Parkinson's disease", the researcher concludes.