Study Rationale: Mitochondria are energy-generating structures vital to the health of all cells. In Parkinson’s disease (PD), mitochondrial dysfunction leads to neuronal degeneration and to the motor and cognitive symptoms of PD. Although preservation of neuronal mitochondria will improve neuronal energy output and prolong the life of neurons, there are currently no agents that target brain mitochondria. In this study, we will examine a new drug mechanism that has shown neuroprotection in preclinical models of PD. This drug targets cardiolipin, a lipid found exclusively in the membranes of mitochondria.
Hypothesis: We hypothesize that the cardiolipin-targeting drug SBT-272 will diminish accumulation of alpha-synuclein and prevent the structural disruption of mitochondrial membranes induced by alpha-synuclein aggregates in preclinical models of PD. This mitigation of cellular pathology should slow disease progression and improve cellular energy production in these PD models.
Study Design: We will treat neurons derived from patient stem cells and a well-characterized preclinical model that exhibits PD like pathology with SBT-272. We will determine whether the compound affects measures of PD symptoms that are clinically meaningful and assess whether this treatment slows the death of brain cells and improves mitochondrial structure and function, including cellular energy production. We will analyze biofluids from the preclinical model and from patient-derived neurons to determine whether we can develop a new method for monitoring PD progression as well as assessing the potential therapeutic benefits in people with PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: SBT-272 could be the first medicine to improve mitochondrial function in people with PD, potentially slowing disease progression and improving neuronal health and motor and cognitive symptoms. We also hope to identify new biomarkers that will allow us to assess mitochondrial function and monitor SBT-272’s ability to slow progression.
Next Steps for Development: Our study is designed to assess potential benefits of SBT-272 in the animal and neuronal PD model and to reveal clinically tractable biomarkers for clinical study design. If successful, we believe this research may also help generate investment support to advance SBT-272 into clinical trials for people with PD.