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 the health care burden on society.
Study Design:
Experiments are planned that will support the advancement of CSM-101 into clinical trials for PD. The primary aim of this work is to evaluate the safety of CSM-101 in preclinical models which will help identify the range of doses that can be used in clinical trials.
Impact on Diagnosis/Treatment of Parkinson’s disease:
CSM-101 is a molecularly-targeted drug with potential to treat multiple forms of PD. Given that the current treatment landscape for PD is focused on alleviating symptoms, TRPML1 and lysosomal activation can offer patients new options that address the true cause of PD.
Next Steps for Development:
Following successful completion of the current study CSM-101 will be administered to healthy volunteers and PD patients as part of a Phase I safety and tolerability trial.