Study Rationale:
Mitochondrial dysfunction (powerhouse of the cell), free-radical induced injury (highly reactive atoms that can be harmful) and inflammatory mechanisms have been proposed to play a key role in the neurodegenerative processes of Parkinson’s disease (PD). Mitochon Pharmaceuticals has demonstrated that a once-a-day oral treatment with MP101, a brain-penetrant mitochondrial modulator, gets rid of free radicals, restoring mitochondrial function and increasing higher levels of a key neuroprotective molecule called brain-derived neurotrophic factor (BDNF). Pre-clinical studies have shown encouraging results with protective effects on preservation of dopamine neurons, which may have disease-modifying effects.
Hypothesis:
This project work will test both MP101 and MP201 (an analog, or chemical with similar structure or function as the original) in a series of comprehensive pre-clinical studies that will evaluate behavioral effects, induction of BDNF and neuronal preservation. It will also examine the effects of these compounds on mitochondria to better understand their mechanistic impact.
Study Design:
This study is designed to evaluate the protective affects of MP101 and MP201 in pre-clinical models of PD injected with a toxin (6’OHDA) that selectively destroys dopamine-producing neurons, the hallmark of PD. The study will look at two outcomes as follows: 1) chronic treatment (two weeks of therapy) administered one day after giving the toxin to evaluate the potential of the drugs to prevent neuronal loss and mimic disease progression; 2) chronic treatment 10 days following toxin administration (allowing for most neurons to die) to determine if the drugs can impact recovery and regrowth of new neurons. In both scenarios, we will measure behavioral effects, brain dopamine levels, neuron counts, BDNF levels and markers of mitochondrial quality.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Parkinson’s is a degenerative disease that, with early intervention, has the potential to be slowed or even prevented. We believe that, by harnessing the power of mitochondria, we can significantly alter disease progression in early-stage PD, and, potentially, offer those with late-stage PD an opportunity to boost neuron regrowth.
Next Steps for Development:
MP101 is in the clinical stage of development and, if these experiments are successful, clinical trials could begin as early as 2019.