Study Rationale: Studies show that Parkinson's disease (PD) is frequently associated with damage to mitochondria, structures that provide cells with the energy they need to function. In particular, a process called mitophagy — which normally removes damaged mitochondria — is impaired in PD. The ensuing loss of quality control leads to the accumulation of dysfunctional mitochondria and degeneration of brain cells. Enhancing mitophagy might therefore restore the function of brain cells that are damaged or lost in PD. One way to boost mitophagy is by inhibiting USP30, a mitochondrial protein that curtails mitophagy.
Hypothesis: We hypothesize that VB-08, a novel molecule that reduces USP30 activity and improves mitophagy, will be safe for testing in human clinical trials per guidelines laid out by the US Food and Drug Administration (FDA).
Study Design: We will perform a battery of tests to determine whether VB-08 can be safely given to animals. We will assess different doses, measure the amount of VB-08 that reaches the blood stream and examine its effects on organs. This work will inform the dose levels that may be appropriate for later clinical testing in people with PD. At the same time, we will develop biomarkers that reveal how VB-08 affects cell functions related to mitophagy. Such biomarkers should be detectable in blood or spinal fluid samples for use in monitoring the effects of VB-08 in humans.
Impact on Diagnosis/Treatment of Parkinson’s disease: Today, no treatment can stop the worsening of PD. VB-08 has the potential to be the first treatment that modifies the progression of PD, rather than merely masking its symptoms. The safety studies here are integral to paving the way for testing VB-08 in people with PD.
Next Steps for Development: Our results will be used to create an “Investigational New Drug” application to the FDA. If approved, VB-08 will be given to healthy individuals in a “first in human” study before being tested in people with PD.