Study Rationale: The appropriate regulation of proteins and lipids within neurons is critical for human health. Lysosomes are specialized structures within cells that are responsible for the removal of damaged proteins and toxic lipids that would otherwise interfere with neuronal function. Research has now shown that lysosomes can be mutated in Parkinson’s disease (PD) thus leading to the drastic accumulation of toxic proteins and lipids which cause neurons to die. TRPML1 is an ion channel on lysosomes and its activation can boost lysosomal functions.
Hypothesis: Development of a safe and effective TRPML1 activating drug called CSM-101 will restore lysosomal functions in PD and will both improve patient quality of life and decrease health care challenges society.
Study Design: Experiments are planned that will support the advancement of TRPML1 agonists into clinical trials for PD. The aim of this work is to evaluate biomarkers of TRPML1 activation in pre-clinical models through use of a brain penetrant agonist, CSM-101.
Impact on Diagnosis/Treatment of Parkinson’s disease: Biomarker identification is critical towards proper evaluation of pre-clinical efficacy studies and identifying the range of doses that can be used in clinical trials. Successful completion of this project will provide critical translational tools to support the clinical development of TRPML1-targeted therapies, ultimately accelerating the path to effective treatments for Parkinson’s and other diseases linked to lysosomal dysfunction.
Next Steps for Development: Following successful completion of the current study, TRPML1 biomarkers will be established for use in healthy volunteers and PD patients in order to facilitate a Phase I safety and tolerability trial.